Hematology News

The peer-review process, which is used by scientific journals to validate legitimate research, is now under legal scrutiny. The US District Court for the Southern District of New York will soon rule on whether scientific publishers have compromised this system for profit. In mid-September, University of California, Los Angeles neuroscientist Lucina Uddin filed a class action lawsuit against six leading academic publishers — Elsevier, Wolters Kluwer, Wiley, Sage Publications, Taylor & Francis, and Springer Nature — accusing them of violating antitrust laws and obstructing academic research.

The lawsuit targets several long-standing practices in scientific publishing, including the lack of compensation for peer reviewers, restrictions that require submitting to only one journal at a time, and bans on sharing manuscripts under review. Uddin’s complaint argues that these practices contribute to inefficiencies in the review process, thus delaying the publication of critical discoveries, which could hinder research, clinical advancements, and the development of new medical treatments.

The suit also noted that these publishers generated $10 billion in revenue in 2023 in peer-reviewed journals. However, the complaint seemingly overlooks the widespread practice of preprint repositories, where many manuscripts are shared while awaiting peer review.
 

Flawed Reviews

A growing number of studies have highlighted subpar or unethical behaviors among reviewers, who are supposed to adhere to the highest standards of methodological rigor, both in conducting research and reviewing work for journals. One recent study published in Scientometrics in August examined 263 reviews from 37 journals across various disciplines and found alarming patterns of duplication. Many of the reviews contained identical or highly similar language. Some reviewers were found to be suggesting that the authors expand their bibliographies to include the reviewers’ own work, thus inflating their citation counts.

As María Ángeles Oviedo-García from the University of Seville in Spain, pointed out: “The analysis of 263 review reports shows a pattern of vague, repetitive statements — often identical or very similar — along with coercive citations, ultimately resulting in misleading reviews.”

Experts in research integrity and ethics argue that while issues persist, the integrity of scientific research is improving. Increasing research and public disclosure reflect a heightened awareness of problems long overlooked.

“There is indeed a problem with research reliability, but it’s not as widespread or severe as some portray,” said Daniele Fanelli, a metascientist at the London School of Economics and Political Science in England. Speaking to this news organization, Fanelli, who has been studying scientific misconduct for about 20 years, noted that while his early work left him disillusioned, further research has replaced his cynicism with what he describes as healthy skepticism and a more optimistic outlook. Fanelli also collaborates with the Luxembourg Agency for Research Integrity and the Advisory Committee on Research Ethics and Bioethics at the Italian National Research Council (CNR), where he helped develop the first research integrity guidelines.
 

Lack of Awareness

A recurring challenge is the difficulty in distinguishing between honest mistakes and intentional misconduct. “This is why greater investment in education is essential,” said Daniel Pizzolato, European Network of Research Ethics Committees, Bonn, Germany, and the Centre for Biomedical Ethics and Law, KU Leuven in Belgium.

While Pizzolato acknowledged that institutions such as the CNR in Italy provide a positive example, awareness of research integrity is generally still lacking across much of Europe, and there are few offices dedicated to promoting research integrity. However, he pointed to promising developments in other countries. “In France and Denmark, researchers are required to be familiar with integrity norms because codes of conduct have legal standing. Some major international funding bodies like the European Molecular Biology Organization are making participation in research integrity courses a condition for receiving grants.”

Pizzolato remains optimistic. “There is a growing willingness to move past this impasse,” he said.

A recent study published in The Journal of Clinical Epidemiology reveals troubling gaps in how retracted biomedical articles are flagged and cited. Led by Caitlin Bakkera, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands, the research sought to determine whether articles retracted because of errors or fraud were properly flagged across various databases.

The results were concerning: Less than 5% of retracted articles had consistent retraction notices across all databases that hosted them, and less than 50% of citations referenced the retraction. None of the 414 retraction notices analyzed met best-practice guidelines for completeness. Bakkera and colleagues warned that these shortcomings threaten the integrity of public health research.
 

Fanelli’s Perspective

Despite the concerns, Fanelli remains calm. “Science is based on debate and a perspective called organized skepticism, which helps reveal the truth,” he explained. “While there is often excessive skepticism today, the overall quality of clinical trials is improving.

“It’s important to remember that reliable results take time and shouldn’t depend on the outcome of a single study. It’s essential to consider the broader context, the history of the research field, and potential conflicts of interest, both financial and otherwise. Biomedical research requires constant updates,” he concluded.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The peer-review process, which is used by scientific journals to validate legitimate research, is now under legal scrutiny. The US District Court for the Southern District of New York will soon rule on whether scientific publishers have compromised this system for profit. In mid-September, University of California, Los Angeles neuroscientist Lucina Uddin filed a class action lawsuit against six leading academic publishers — Elsevier, Wolters Kluwer, Wiley, Sage Publications, Taylor & Francis, and Springer Nature — accusing them of violating antitrust laws and obstructing academic research.

The lawsuit targets several long-standing practices in scientific publishing, including the lack of compensation for peer reviewers, restrictions that require submitting to only one journal at a time, and bans on sharing manuscripts under review. Uddin’s complaint argues that these practices contribute to inefficiencies in the review process, thus delaying the publication of critical discoveries, which could hinder research, clinical advancements, and the development of new medical treatments.

The suit also noted that these publishers generated $10 billion in revenue in 2023 in peer-reviewed journals. However, the complaint seemingly overlooks the widespread practice of preprint repositories, where many manuscripts are shared while awaiting peer review.
 

Flawed Reviews

A growing number of studies have highlighted subpar or unethical behaviors among reviewers, who are supposed to adhere to the highest standards of methodological rigor, both in conducting research and reviewing work for journals. One recent study published in Scientometrics in August examined 263 reviews from 37 journals across various disciplines and found alarming patterns of duplication. Many of the reviews contained identical or highly similar language. Some reviewers were found to be suggesting that the authors expand their bibliographies to include the reviewers’ own work, thus inflating their citation counts.

As María Ángeles Oviedo-García from the University of Seville in Spain, pointed out: “The analysis of 263 review reports shows a pattern of vague, repetitive statements — often identical or very similar — along with coercive citations, ultimately resulting in misleading reviews.”

Experts in research integrity and ethics argue that while issues persist, the integrity of scientific research is improving. Increasing research and public disclosure reflect a heightened awareness of problems long overlooked.

“There is indeed a problem with research reliability, but it’s not as widespread or severe as some portray,” said Daniele Fanelli, a metascientist at the London School of Economics and Political Science in England. Speaking to this news organization, Fanelli, who has been studying scientific misconduct for about 20 years, noted that while his early work left him disillusioned, further research has replaced his cynicism with what he describes as healthy skepticism and a more optimistic outlook. Fanelli also collaborates with the Luxembourg Agency for Research Integrity and the Advisory Committee on Research Ethics and Bioethics at the Italian National Research Council (CNR), where he helped develop the first research integrity guidelines.
 

Lack of Awareness

A recurring challenge is the difficulty in distinguishing between honest mistakes and intentional misconduct. “This is why greater investment in education is essential,” said Daniel Pizzolato, European Network of Research Ethics Committees, Bonn, Germany, and the Centre for Biomedical Ethics and Law, KU Leuven in Belgium.

While Pizzolato acknowledged that institutions such as the CNR in Italy provide a positive example, awareness of research integrity is generally still lacking across much of Europe, and there are few offices dedicated to promoting research integrity. However, he pointed to promising developments in other countries. “In France and Denmark, researchers are required to be familiar with integrity norms because codes of conduct have legal standing. Some major international funding bodies like the European Molecular Biology Organization are making participation in research integrity courses a condition for receiving grants.”

Pizzolato remains optimistic. “There is a growing willingness to move past this impasse,” he said.

A recent study published in The Journal of Clinical Epidemiology reveals troubling gaps in how retracted biomedical articles are flagged and cited. Led by Caitlin Bakkera, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands, the research sought to determine whether articles retracted because of errors or fraud were properly flagged across various databases.

The results were concerning: Less than 5% of retracted articles had consistent retraction notices across all databases that hosted them, and less than 50% of citations referenced the retraction. None of the 414 retraction notices analyzed met best-practice guidelines for completeness. Bakkera and colleagues warned that these shortcomings threaten the integrity of public health research.
 

Fanelli’s Perspective

Despite the concerns, Fanelli remains calm. “Science is based on debate and a perspective called organized skepticism, which helps reveal the truth,” he explained. “While there is often excessive skepticism today, the overall quality of clinical trials is improving.

“It’s important to remember that reliable results take time and shouldn’t depend on the outcome of a single study. It’s essential to consider the broader context, the history of the research field, and potential conflicts of interest, both financial and otherwise. Biomedical research requires constant updates,” he concluded.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The peer-review process, which is used by scientific journals to validate legitimate research, is now under legal scrutiny. The US District Court for the Southern District of New York will soon rule on whether scientific publishers have compromised this system for profit. In mid-September, University of California, Los Angeles neuroscientist Lucina Uddin filed a class action lawsuit against six leading academic publishers — Elsevier, Wolters Kluwer, Wiley, Sage Publications, Taylor & Francis, and Springer Nature — accusing them of violating antitrust laws and obstructing academic research.

The lawsuit targets several long-standing practices in scientific publishing, including the lack of compensation for peer reviewers, restrictions that require submitting to only one journal at a time, and bans on sharing manuscripts under review. Uddin’s complaint argues that these practices contribute to inefficiencies in the review process, thus delaying the publication of critical discoveries, which could hinder research, clinical advancements, and the development of new medical treatments.

The suit also noted that these publishers generated $10 billion in revenue in 2023 in peer-reviewed journals. However, the complaint seemingly overlooks the widespread practice of preprint repositories, where many manuscripts are shared while awaiting peer review.
 

Flawed Reviews

A growing number of studies have highlighted subpar or unethical behaviors among reviewers, who are supposed to adhere to the highest standards of methodological rigor, both in conducting research and reviewing work for journals. One recent study published in Scientometrics in August examined 263 reviews from 37 journals across various disciplines and found alarming patterns of duplication. Many of the reviews contained identical or highly similar language. Some reviewers were found to be suggesting that the authors expand their bibliographies to include the reviewers’ own work, thus inflating their citation counts.

As María Ángeles Oviedo-García from the University of Seville in Spain, pointed out: “The analysis of 263 review reports shows a pattern of vague, repetitive statements — often identical or very similar — along with coercive citations, ultimately resulting in misleading reviews.”

Experts in research integrity and ethics argue that while issues persist, the integrity of scientific research is improving. Increasing research and public disclosure reflect a heightened awareness of problems long overlooked.

“There is indeed a problem with research reliability, but it’s not as widespread or severe as some portray,” said Daniele Fanelli, a metascientist at the London School of Economics and Political Science in England. Speaking to this news organization, Fanelli, who has been studying scientific misconduct for about 20 years, noted that while his early work left him disillusioned, further research has replaced his cynicism with what he describes as healthy skepticism and a more optimistic outlook. Fanelli also collaborates with the Luxembourg Agency for Research Integrity and the Advisory Committee on Research Ethics and Bioethics at the Italian National Research Council (CNR), where he helped develop the first research integrity guidelines.
 

Lack of Awareness

A recurring challenge is the difficulty in distinguishing between honest mistakes and intentional misconduct. “This is why greater investment in education is essential,” said Daniel Pizzolato, European Network of Research Ethics Committees, Bonn, Germany, and the Centre for Biomedical Ethics and Law, KU Leuven in Belgium.

While Pizzolato acknowledged that institutions such as the CNR in Italy provide a positive example, awareness of research integrity is generally still lacking across much of Europe, and there are few offices dedicated to promoting research integrity. However, he pointed to promising developments in other countries. “In France and Denmark, researchers are required to be familiar with integrity norms because codes of conduct have legal standing. Some major international funding bodies like the European Molecular Biology Organization are making participation in research integrity courses a condition for receiving grants.”

Pizzolato remains optimistic. “There is a growing willingness to move past this impasse,” he said.

A recent study published in The Journal of Clinical Epidemiology reveals troubling gaps in how retracted biomedical articles are flagged and cited. Led by Caitlin Bakkera, Department of Epidemiology, Maastricht University, Maastricht, the Netherlands, the research sought to determine whether articles retracted because of errors or fraud were properly flagged across various databases.

The results were concerning: Less than 5% of retracted articles had consistent retraction notices across all databases that hosted them, and less than 50% of citations referenced the retraction. None of the 414 retraction notices analyzed met best-practice guidelines for completeness. Bakkera and colleagues warned that these shortcomings threaten the integrity of public health research.
 

Fanelli’s Perspective

Despite the concerns, Fanelli remains calm. “Science is based on debate and a perspective called organized skepticism, which helps reveal the truth,” he explained. “While there is often excessive skepticism today, the overall quality of clinical trials is improving.

“It’s important to remember that reliable results take time and shouldn’t depend on the outcome of a single study. It’s essential to consider the broader context, the history of the research field, and potential conflicts of interest, both financial and otherwise. Biomedical research requires constant updates,” he concluded.

This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

A version of this article first appeared on Medscape.com.

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

A version of this article first appeared on Medscape.com.

HUNTINGTON BEACH, CALIFORNIA — When patients of Aaron Mangold, MD, first learn they have mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma (CTCL), some are concerned about whether the diagnosis means a shortened life expectancy.

“In most cases, mycosis fungoides will not shorten one’s life, but it can cause significant symptoms,” Dr. Mangold, codirector of the multidisciplinary cutaneous lymphoma clinic at Mayo Clinic, Scottsdale, Arizona, said at the annual meeting of the Pacific Dermatologic Association. “For early-stage disease, I think of it more like diabetes; this is really a chronic disease” that unlikely will be fatal but may be associated with increased morbidity as the disease progresses, and “the overall goal of therapy should be disease control to increase quality of life.”

courtesy Dr. Aaron Mangold

Patient- and lymphoma-specific factors drive the choice of therapy. The focus for patients with early-stage disease, Dr. Mangold said, is to treat comorbidities and symptoms, such as itch or skin pain, maximize their quality of life, and consider the potential for associated toxicities of therapy as the disease progresses. Start with the least toxic, targeted, nonimmunosuppressive therapy, “then work toward more toxic immunosuppressive therapies,” he advised. “Use toxic agents just long enough to control the disease, then transition to a maintenance regimen with less toxic immunosuppressive agents.”
 

When Close Follow-Up Is Advised

According to unpublished data from PROCLIPI (the Prospective Cutaneous Lymphoma International Prognostic Index) study presented at the fifth World Congress of Cutaneous Lymphomas earlier in 2024, the following factors warrant consideration for close follow-up and more aggressive treatment: Nodal enlargement greater than 15 mm, age over 60 years, presence of plaques, and large-cell transformation in skin. “These are some of the stigmata in early disease that might guide you toward referring” a patient to a CTCL expert, Dr. Mangold said. (Consensus-based recommendations on the management of MF in children were published in August of 2024.)

According to Dr. Mangold, topical/skin-directed therapies are best for early-stage disease or in combination with systemic therapies in advanced disease. For early-stage disease, one of his preferred options is daily application of a skin moisturizer plus a topical corticosteroid such as clobetasol, halobetasol, or augmented betamethasone, then evaluating the response at 3 months. “This is a cheap option, and we see response rates as high as 90%,” he said. “I don’t often see steroid atrophy when treating patients with active MF. There’s a tendency to think, ‘I don’t want to overtreat.’ I think you can be aggressive. If you look in the literature, people typically pulse twice daily for a couple of weeks with a 1-week break.”

Mechlorethamine, a topical alkylating gel approved in 2013 for the treatment of early-stage MF, is an option when patients fail to respond to topical steroids, prefer to avoid steroids, or have thick, plaque-like disease. With mechlorethamine, it is important to “start slow and be patient,” Dr. Mangold said. “Real-world data shows that it takes 12-18 months to get a good response. Counsel patients that they are likely to get a rash, and that the risk of rash is dose dependent.”

Other treatment options to consider include imiquimod, which can be used for single refractory spots. He typically recommends application 5 days per week with titration up to daily if tolerated for up to 3 months. “Treat until you get a brisk immune response,” he said. “We’ve seen patients with durable, long-term responses.”
 

UVB Phototherapy Effective

For patients with stage IB disease, topical therapies are less practical and may be focused on refractory areas of disease. Narrow-band UVB phototherapy is the most practical and cost-effective treatment, Dr. Mangold said. Earlier-stage patch disease responds to phototherapy in up to 80% of cases, while plaque-stage disease responds in up to half of cases. “More frequent use of phototherapy may decrease time to clearance, but overall response is similar.”

Dr. Mangold recommends phototherapy 2-3 days per week, titrating up to a maximal response dose, and maintaining that dose for about 3 months. Maintenance involves tapering the phototherapy dose to a minimal dose with continued response. “The goal is to prevent relapse,” he said.

For patients with MF of stage IIB and higher, he considers total skin electron beam therapy, an oral retinoid with phototherapy, systemic agents, and focal radiation with systemic treatment. One of his go-to systemic options is bexarotene, which he uses for early-stage disease refractory to treatment or for less aggressive advanced disease. “We typically use a low dose ... and about half of patients respond,” Dr. Mangold said. The time to response is about 6 months. Bexarotene causes elevated lipids and low thyroid function, so he initiates patients on fenofibrate and levothyroxine at baseline.

Another systemic option is brentuximab vedotin, a monoclonal antibody that targets cells with CD30 expression, which is typically administered in a specialty center every 3 weeks for up to 16 cycles. “In practice, we often use six to eight cycles to avoid neuropathy,” he said. “It’s a good debulking agent, the time to response is 6-9 weeks, and it has a sustained response of 60%.” Neuropathy can occur with treatment, but improves over time.

Other systemic options for MF include romidepsin, mogamulizumab, and extracorporeal photopheresis used in erythrodermic disease.
 

Radiation An Option in Some Cases

Dr. Mangold noted that low doses of radiation therapy can effectively treat MF lesions in as little as one dose. “We can use it as a cure for a single spot or to temporarily treat the disease while other therapies are being started,” he said. Long-term side effects need to be considered when using radiation. “The more radiation, the more side effects.”

Dr. Mangold disclosed that he is an investigator for Sun Pharmaceutical, Solagenix, Elorac, miRagen, Kyowa Kirin, the National Clinical Trials Network, and CRISPR Therapeutics. He has also received consulting fees/honoraria from Kirin and Solagenix.

A version of this article first appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

A version of this article first appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

A version of this article first appeared on Medscape.com.

A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI, Janssen Biotech, Inc.), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study.

“Cilta-cel is the first CAR T-cell therapy to demonstrate an overall survival benefit in multiple myeloma,” María-Victoria Mateos, MD, PhD, said during a presentation of the updated CARTITUDE-4 data at the annual meeting of the International Myeloma Society in late September.

A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Dr. Mateos, a professor at the University Hospital of Salamanca, Spain.

The significant OS benefit was sustained across all prespecified subgroups, she noted.

The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy.

“CARVYKTI demonstrated remarkable efficacy as a personalized, one-time infusion in the earlier treatment of relapsed/refractory multiple myeloma as shown through the CARTITUDE-4 study results,” study coauthor Binod Dhakal, MD, of the Medical College of Wisconsin, in Milwaukee, stated in a press release announcing that expansion. “With this approval, I’m excited for patients who may have the opportunity for a treatment-free period for their multiple myeloma as early as first relapse, with the hope of eliminating the burden of having to be on continuous treatment while living with this challenging disease.”

At the latest analysis, PFS was not reached in the cilta-cel arm and was 11.79 months with SoC, Dr. Mateos said.

The 30-month PFS rates were 59% and 26%, respectively (HR, 0.29), and the PFS benefit was observed across prespecified subgroups.

Patients in the cilta-cel arm also had better complete response rates (77% vs 24%), overall response rates (85% vs 67%), and minimal residual disease-negativity rates (62% vs 18%).

Median duration of response was not reached with cilta-cel and was 18.69 months with SoC, and median time to symptom worsening was not reached vs 34.33 months, respectively.

Safety at the latest update was consistent with prior analyses.

The CARTITUDE findings continue to support the overall benefit-risk profile of cilta-cel vs SoC in patients with lenalidomide-refractory multiple myeloma as early as after the first relapse, Dr. Mateos concluded.

Despite the “compelling efficacy” of cilta-cel, there remains a need for “a safer and equally (if not more) effective CAR-T product” in this setting, Manni Mohyuddin, MD, told this news organization.

“The trial does not change my practice,” said Dr. Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City.

“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.

“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”

Toxicity is also a concern, he said.

“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.

For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.

“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.”

Dr. Mateos reported relationships with AbbVie, Amgen, BMS, GSK, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline Therapeutics, and Takeda. Dr. Mohyuddin had no disclosures.
 

A version of this article first appeared on Medscape.com.

In the treatment of patients with newly diagnosed multiple myeloma (MM) who are not eligible for stem cell transplant or are transplant-deferred, adding subcutaneous daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) significantly improves minimal residual disease (MRD) outcomes among patients, the first results from the phase 3 CEPHEUS trial showed.

“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.

“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”

For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.

However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.

For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).

In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.

The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.

Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.

The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.

For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).

Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).

A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.

A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).

There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.

Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.

The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.

In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.

Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.

Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.

“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”

Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.

“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.

“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”

He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”

Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”

“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.

“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.

Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
 

A version of this article first appeared on Medscape.com.

In the treatment of patients with newly diagnosed multiple myeloma (MM) who are not eligible for stem cell transplant or are transplant-deferred, adding subcutaneous daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) significantly improves minimal residual disease (MRD) outcomes among patients, the first results from the phase 3 CEPHEUS trial showed.

“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.

“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”

For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.

However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.

For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).

In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.

The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.

Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.

The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.

For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).

Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).

A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.

A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).

There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.

Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.

The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.

In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.

Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.

Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.

“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”

Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.

“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.

“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”

He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”

Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”

“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.

“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.

Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
 

A version of this article first appeared on Medscape.com.

In the treatment of patients with newly diagnosed multiple myeloma (MM) who are not eligible for stem cell transplant or are transplant-deferred, adding subcutaneous daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) significantly improves minimal residual disease (MRD) outcomes among patients, the first results from the phase 3 CEPHEUS trial showed.

“CEPHEUS is the first phase 3 daratumumab trial with a primary endpoint of MRD negativity,” said first author Saad Z. Usmani, MD, of Memorial Sloan Kettering Cancer Center, New York City, in presenting late-breaking findings at the annual meeting of the International Myeloma Society in Rio de Janeiro, Brazil in late September.

“We found that adding daratumumab to VRd significantly improved depth and duration of response,” Dr. Usmani said. “[The quadruplet regimen] has the potential to improve clinical outcomes for transplant-ineligible or transplant-deferred patients with newly diagnosed MM who can tolerate bortezomib.”

For newly diagnosed patients with MM who are not eligible for a stem cell transplant, the triplet MAIA regimen of daratumumab, lenalidomide, and dexamethasone is a recommended standard of care, having shown a median overall survival of 7.5 years.

However, for those who are transplant eligible, the PERSEUS regimen of D-VRd followed by daratumumab/lenalidomide maintenance, has shown significant progress-free survival benefits compared with the standard of care.

For the ongoing, multicenter, open-label CEPHEUS study, Dr. Usmani and his colleagues investigated the efficacy of the quadruplet D-VRd regimen compared with VRd alone among newly diagnosed patients who are transplant-ineligible or deferred (not planned as initial therapy).

In the trial, 395 adult patients with transplant-ineligible or transplant-deferred newly diagnosed MM all were initially treated with eight 21-day cycles of VRd, followed by 28-day cycles of lenalidomide until disease progression.

The patients were then randomized to VRd either with (n = 197) or without (n = 198) subcutaneous daratumumab.

Those receiving daratumumab received the subcutaneous therapy weekly in cycles 1 and 2, every 3 weeks in cycles 3-8, and every 4 weeks in cycles 9 or more, until disease progression.

The patients had a median age of 70 years; 28.1% had International Staging System stage III disease, and 13.2% had high-risk cytogenetics.

For the primary endpoint, with a median follow-up of 58.7 months, those in the daratumumab group had a significantly higher rate of being MRD-negative (60.9%) than the VRd-only group (39.4%; odds ratio [OR], 2.37; P < .0001).

Likewise, progression-free survival (PFS) was significantly improved with the daratumumab regimen vs VRd (hazard ratio [HR], 0.57; P = .0005).

A median PFS was not reached for daratumumab plus VRd, compared with 52.6 months for the VRd group, while estimated 54-month PFS rates were 68.1% vs 49.5%, respectively.

A complete response or better was achieved among 81.2% in the daratumumab regimen vs 61.6% with VRd alone (P < .0001) and a sustained rate of MRD-negativity was achieved in 48.7% vs 26.3%, respectively (P < .0001).

There was a trend of overall survival in favor of daratumumab plus VRd (HR, 0.85), with an HR of 0.69 in a sensitivity analysis adjusting for deaths related to COVID-19.

Patients in the daratumumab group had a substantially longer median duration of treatment (56.3 months) than the VRd-only group (34.3 months), with the most common reason for treatment discontinuation being disease progression.

The benefit of daratumumab was generally consistent across the study’s prespecified subgroups, and the relative dose intensity of VRd was not affected by combination with daratumumab.

In terms of safety, treatment-emergent adverse events (TEAEs) were consistent with the known profile of daratumumab and VRd, with grade 5 TEAEs comparable between the two groups after adjusting for treatment exposure.

Quality of life, as measured by EORTC QLQ-C30 score, was improved in both arms over time, with no detriment related to treatment with daratumumab.

Of note, frail patients were not included in the trial. Asked in the Q and A why they were excluded, Dr. Usmani explained that “all of these options are wonderful for our patients, and we are entering a phase where quadruplet therapies will become a mainstay for majority of patients.

“But we have to be careful as we think about not overtreating patients or giving too many side effects of therapies, and that’s why it made sense for us to exclude the frail patients.”

Along those lines, he noted that a key concern in the CEPHEUS trial was tolerance of bortezomib.

“Peripheral sensory neuropathy tends to occur in about half of the patients receiving bortezomib, and about half of that number is grade 2 or higher,” he noted in an interview.

“In some patients, the symptoms do not completely resolve. [Therefore], in transplant-ineligible patients, quadruple regimens may be more relevant for the fit or intermediate-fit patients.”

He concluded that “the CEPHEUS trial compliments the MAIA regimen in supporting a daratumumab-based quadruplet or triplet standard-of-care option across transplant-ineligible patients and those deferring transplant.”

Commenting on the study, Philippe Moreau, MD, who is president of the IMS, noted that “the CEPHEUS study is important because [determining] the best treatment upfront for elderly patients is very important.”

“We need confirmation of the very good results achieved with the IMROZ trial, which showed an estimated 5-year PFS of 63.2%, said Dr. Moreau, professor of clinical hematology and head of the translational research program in hematology and oncology at the University Hospital of Nantes, France.

“If we can achieve the same results, we will have the confirmation that quadruplet is probably here to stay,” Dr. Moreau said.

Dr. Usmani disclosed relationships with Abbvie, Amgen, BioPharma, Bristol Myers Squibb, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineOx, and Takeda.
 

A version of this article first appeared on Medscape.com.

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

A version of this article first appeared on Medscape.com.

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

A version of this article first appeared on Medscape.com.

Salaries for millennial physicians are slightly increasing, but clinicians still face pay disparities across location, practice type, and gender.

Medscape Medical News reviewed survey data from more than 1200 practicing doctors under age 40 across 29 specialties over a 4-month period starting in October 2023.

The average annual total compensation (including any bonuses) for young clinicians rose from $326,000 to $338,000, about 4%, between 2022 and 2023. Among millennials, primary care physicians saw a 5% increase. But a large pay gap exists between fields: Specialists under age 40 earned an average of $357,000 in 2023, compared with the average primary care clinician salary of $271,000.

“Procedures are reimbursed too high, while very little value is placed on primary care,” one survey respondent complained.

The type of practice plays a major part in compensation. Millennial doctors in office-based, single-specialty group practices earned an average of $358,000 per year, followed by those in office-based multispecialty group practices at 355,000 per year. Those in outpatient clinics earned $278,000 per year.

“I believe the practice situation is a huge portion of compensation,” said Tiffany Di Pietro, DO, a cardiologist and internal medicine physician in Fort Lauderdale, Florida. “Owning your own private practice is generally more lucrative (if you have good business sense), but it is also quite a bit more time-consuming, whereas employed physicians usually make less but have fewer concerns with staffing and overhead.”

Like in previous years, a gender pay gap equated to men outearning women. Female physicians under age 40 of any kind earned about $302,000 per year, 24% less than their male counterparts, on average.

Millennial doctors in the Midwest brought home the biggest earnings, with an average salary of $343,000 vs $332,000 on the West Coast.

Millennial physicians also reported higher levels of dissatisfaction. In the 2022 report, 46% said they were not paid fairly. That figure rose to 49%. Just 68% of millennial doctors would choose medicine again if they could do things over, down from 76% in the 2021 report.

“Doctors go through multiple years of school and then have to act like we are working at Dunkin’ Donuts — like we’re on an assembly line,” one survey respondent said. “We should not have to be paid per patient seen but valued for 8-9 years of training.”

Despite these complaints, close to 7 out of 10 millennial respondents said pay was not a major factor in what area of medicine they chose, with 29% saying it played no role at all in their decision.

Psychiatrists and anesthesiologists were the happiest with their earnings, with 61% of both specialties reporting that they felt fairly paid. They were followed by dermatologists and emergency medicine doctors, both of whom 60% reported fair earnings.

Many millennial doctors are finding ways to make money outside of their practice, with 18% securing other medical-related work, 15% doing medical moonlighting, and 5% taking on non–medical-related work.

A version of this article first appeared on Medscape.com.

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

A version of this article first appeared on Medscape.com.

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

A version of this article first appeared on Medscape.com.

Fantine Giap, MD, sat across from a 21-year-old with a rare sarcoma at the base of her skull. 

Despite the large tumor, nestled in a sensitive area, the Boston-based radiation oncologist could envision a bright future for her patient. 

She and the other members of the patient’s care team had an impressive cancer-fighting arsenal at her fingertips. The team had recommended surgery, followed by proton therapy — a sophisticated tool able to deliver concentrated, razor-focused radiation to the once apple-sized growth, while sparing the fragile brain stem, optic nerve, and spinal cord. 

Surgery went as planned. But as the days and weeks wore on and insurance prior authorization for the proton therapy never came, the tumor roared back, leading to more surgeries and more complications. Ultimately, the young woman needed a tracheostomy and a feeding tube. 

By the time insurance said yes, more than 1 year from her initial visit, the future the team had envisioned seemed out of reach. 

“Unfortunately for this patient, it went from a potentially curable situation to a likely not curable situation,” recalled Dr. Giap, a clinician at Massachusetts General Hospital and instructor at Harvard Medical School, Boston. “I wanted to cry every day that she waited.’’ 

While a stark example, such insurance delays are not uncommon, according to new research published in JAMA Network Open.

The study of 206 denials in radiation oncology concluded that more than two-thirds were ultimately approved on appeal without changes, but often these approvals came only after costly delays that potentially compromised patient care.

Other studies have found that number to be even higher, with more than 86% of prior authorization requests ultimately approved with few changes.

‘’It gives you the idea that this entire process might be a little futile — that it’s just wasting people’s time,’’ said Fumiko Chino, MD, coauthor on the JAMA study and now an assistant professor in radiation oncology at MD Anderson Cancer Center in Houston. ‘’The problem is cancer doesn’t wait for bureaucracy.’’
 

Barriers at Every Step

As Dr. Chino and her study coauthors explained, advancements like intensity-modulated radiation therapy and stereotactic radiosurgery have allowed a new generation of specialists to treat previously untreatable cancers in ways that maximize tumor-killing power while minimizing collateral damage. But these tools require sophisticated planning, imaging, simulations and execution — all of which are subject to increased insurance scrutiny.

‘’We face barriers pretty much every step of the way for every patient,’’ said Dr. Chino.

To investigate how such barriers impact care, Dr. Chino and colleagues at Memorial Sloan Kettering Cancer Center — where she worked until July — looked at 206 cases in which payers denied prior authorization for radiation therapy from November 1, 2021 to December 8, 2022. 

The team found that 62% were ultimately approved without any change to technique or dose, while 28% were authorized, but with lower doses or less sophisticated techniques. Four people, however, never got authorization at all — three abandoned treatment altogether, and one sought treatment at another institution.

Treatment delays ranged from 1 day to 49 days. Eighty-three patients died.

Would some of them have lived if it weren’t for prior authorization?

Dr. Chino cannot say for sure, but did note that certain cancers, like cervical cancer, can grow so quickly that every day of delayed treatment makes them harder to control. 

Patients with metastatic or late-stage cancers are often denied more aggressive treatments by insurers who, in essence, “assume that they are going to die from their disease anyway,” Dr. Chino said. 

She views this as tragically shortsighted.

‘’There’s actually a strong body of evidence to show that if you treat even metastatic stage IV diseases aggressively, you can prolong not just quality of life but also quantity,’’ she said. 

In cases where the cancer is more localized and insurance mandates lower doses or cheaper techniques, the consequences can be equally heartbreaking.

‘’It’s like saying instead of taking an extra-strength Tylenol you can only have a baby aspirin,’’ she said. ‘’Their pain is less likely to be controlled, their disease is less likely to be controlled, and they are more likely to need retreatment.’’

Prior authorization delays can also significantly stress patients at the most vulnerable point of their lives.

In another recent study, Dr. Chino found that 69% of patients with cancer reported prior authorization-related delays in care, with one-third waiting a month or longer. One in five never got the care their doctors recommended, and 20% reported spending more than 11 hours on the phone haggling with their insurance companies. 

Most patients rated the process as ‘’bad’’ or ‘’horrible,’’ and said it fueled anxiety.

Such delays can be hard on clinicians and the healthcare system too. 

One 2022 study found that a typical academic radiation oncology practice spent about a half-million dollars per year seeking insurance preauthorization. Nationally, that number exceeds $40 million.

Then there is the burnout factor. 

Dr. Giap, an early-career physician who specializes in rare, aggressive sarcomas, works at an institution that helped pioneer proton therapy. She says it pains her to tell a desperate patient, like the 21-year-old, who has traveled to her from out of state that they have to wait. 

‘’Knowing that the majority of the cases are ultimately approved and that this wait is often unnecessary makes it even tougher,’’ she said.

Dr. Chino, a breast cancer specialist, has taken to warning patients before the alarming insurance letter arrives in the mail that their insurance may delay authorizing their care. But she tells patients that she will do everything she can to fight for them and develops a back-up plan to pivot to quickly, if needed.

‘’No one goes into medicine to spend their time talking to insurance companies,’’ said Dr. Chino.

The national trade group, America’s Health Insurance Plans (AHIP), did not return repeated requests for an interview for this story. But their official position, as stated on their website, is that “prior authorization is one of many tools health insurance providers use to promote safe, timely, evidence-based, affordable, and efficient care.”

Both Dr. Giap and Dr. Chino believe that prior authorization was developed with good intentions: to save healthcare costs and rein in treatments that don’t necessarily benefit patients. 

But, in their specialty, the burden has proliferated to a point that Dr. Chino characterizes as ‘’unconscionable.’’

She believes that policy changes like the proposed Improving Seniors’ Timely Access to Care Act — which would require real-time decisions for procedures that are routinely approved — could go a long way in improving patient care.

Meanwhile, Dr. Giap said, more research and professional guidelines are necessary to bolster insurance company confidence in newer technologies, particularly for rare cancers.

Her patient ultimately got her proton therapy and is ‘’doing relatively well, all things considered.’’

But not all the stories end like this.

Dr. Chino will never forget a patient with a cancer growing so rapidly she could see it protruding through her chest wall. She called for an urgent PET scan to see where else in the body the cancer might be brewing and rushed the planning process for radiation therapy, both of which faced prior authorization barriers. That scan — which ultimately showed the cancer had spread — was delayed for months.*

If the team had had those imaging results upfront, she said, they would have recommended a completely different course of treatment.

And her patient might be alive today.

‘’Unfortunately,” Dr. Chino said, “the people with the very worst prior authorization stories aren’t here anymore to tell you about them.”

*Correction,  10/4/24: An earlier version of this article erroneously stated that Dr. Chino called for surgery for her patient. She actually called for a PET scan and an urgent radiation start.

A version of this article first appeared on Medscape.com.

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

A version of this article first appeared on Medscape.com.

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

A version of this article first appeared on Medscape.com.

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

A version of this article first appeared on Medscape.com.

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

A version of this article first appeared on Medscape.com.

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

A version of this article first appeared on Medscape.com.

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

A version of this article first appeared on Medscape.com.

RIO DE JANEIRO — The addition of daratumumab to lenalidomide maintenance therapy following autologous stem cell transplant (ASCT) significantly improves rates of achieving minimal residual disease (MRD) negativity and progression-free survival (PFS) among patients newly diagnosed with multiple myeloma (MM), new research showed.

“To date, no randomized trial has directly compared daratumumab-based maintenance therapy vs standard of care lenalidomide maintenance, which is the focus of our trial,” said first author Ashraf Z. Badros, MD, a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, in presenting the findings at the International Myeloma Society (IMS) 2024.

“These results support the addition of daratumumab not only to induction/consolidation but also to standard of care lenalidomide maintenance for these patients,” he said of the study, which was published concurrently in the journal Blood.

Despite ongoing advancements in regimens for induction, consolidation, and maintenance posttransplant, most patients with MM eventually relapse, driving continuing efforts to optimize treatment strategies and improve long-term outcomes.

While daratumumab, an anti-CD38 monoclonal antibody, is approved in induction and consolidation with ASCT for patients with newly diagnosed MM, the authors sought to investigate the potential benefits of adding it to the standard-of-care therapy lenalidomide in maintenance therapy.

For the phase 3 AURIGA trial, they recruited 200 patients with newly diagnosed MM within 12 months of induction therapy and 6 months of ASCT.

The patients, who were all anti-CD38 naive, received at least four induction cycles, had at least a very good partial response, and were MRD positive following ASCT.

They were randomized 1:1 to receive 28-day lenalidomide maintenance cycles either with (n = 99) or without (n = 101) subcutaneous daratumumab for at least 36 cycles or until disease progression, unacceptable toxicity, or withdrawal.

The patients had similar baseline demographic characteristics; their median age was about 62 years, and 25.3% in the daratumumab and 23.5% in the no-daratumumab group had ISS stage III disease. At the time of diagnosis, 23.9% and 16.9%, respectively, had high cytogenic risk.

Overall, patients received a median of five induction cycles prior to entering the study.

For the primary endpoint, the rate of conversion from MRD positive to MRD negative (at a sensitivity of 10-5 using next-generation sequencing) by 12 months was significantly higher in the daratumumab group than in the lenalidomide-only group, at 50.5% vs 18.8% (odds ratio [OR], 4.51; P < .0001).

A similar benefit with the daratumumab group was observed across all clinically relevant subgroups, including patients with high-risk disease.

The MRD-negative conversion rate was similar at the 10-6 threshold (23.2% vs 5%; OR, 5.97; P = .0002).

At a median follow-up of 32.3 months, the overall rates of MRD negativity were 60.6% and 27.7%, with and without daratumumab, respectively (OR, 4.12; P < .0001)

The achievement of complete response or better also was significantly greater with daratumumab (75.8% vs 61.4%; OR, 2.00; P = .0255).

Likewise, PFS favored daratumumab (hazard ratio, 0.53), and the estimated 30-month PFS rates were 82.7% and 66.4%, respectively.

The daratumumab group received more maintenance cycles than the lenalidomide-only group (median of 33 vs 21.5), and it had higher rates of completion of 12 cycles (88.5% vs 78.6%). Dr. Badros noted that the main reason for discontinuation of therapy in the no-daratumumab arm was disease progression.

Consistent with previous studies, daratumumab was associated with more grade 3/4 treatment-emergent adverse events (TEAEs), occurring in 74.0% patients vs 67.3% patients not receiving daratumumab, including infections (18.8% vs 13.3%), cytopenia (54.2% vs 46.9%), and neutropenia (46.9% vs 41.8%). Dr. Badros noted the significantly longer time of treatment in the daratumumab arm (30 months vs 20 months).

Serious TEAEs occurred in 30.2% daratumumab patients and 22.4% no-daratumumab patients, and fatal TEAEs occurred in 2.1% and 1.0% patients, respectively.

“Overall, there were no new safety concerns for daratumumab,” he said.

The authors noted that the requirement that patients be anti-CD38 naive was partially because of “the D-VRd [daratumumab combined with bortezomib, lenalidomide, and dexamethasone] regimen gaining popularity and increased utilization in the myeloma community for transplant-eligible patients with NDMM, even before the publication of the long-term results of the randomized GRIFFIN and PERSEUS studies.”

A key question, remarked Joseph Mikhael, MD, who is chief medical officer of the International Myeloma Foundation, from the audience, is how applicable the findings are in the modern environment, where most patients now have indeed had prior anti-CD38 treatment.

In response, Dr. Badros explained that “I think this is an important study because it is probably one of the few studies that separates the impact of daratumumab-lenalidomide without prior daratumumab use.”

Dr. Badros noted that results from the PERSEUS trial, of D-VRd, show MRD-positive to MRD-negative conversion rates that are similar to the current trial; “therefore, I really don’t think that using daratumumab up front will prevent using it as maintenance,” he said. “If anything, it actually improves outcomes.”

The findings from continuous treatment “are an important reminder that high-risk patients do not do well if you stop treatment,” he said.

Further commenting on the research at the meeting, María-Victoria Mateos, MD, PhD, an associate professor of medicine at the University of Salamanca in Spain, noted that “the unmet need in maintenance is to upgrade the quality of the response and to increase the conversion of MRD-positivity to MRD negative in order to delay the progression of the disease and prolong the overall survival.”

Regarding the AURIGA trial, “this is very interesting data about the role of daratumumab-lenalidomide maintenance in patients who are MRD positive after autologous stem cell transplantation.”

“What is more important is we are progressing in response-adaptive therapy, and we are generating very useful information to possibly make the majority of patients become MRD negative.

“Developing early endpoints as surrogate markers for long-term outcomes and overall survival is critically important,” she added. “Otherwise, trials may continue for more than 15 years.”

The study was sponsored by Janssen Biotech. Dr. Badros reported relationships with Bristol-Myers Squibb, BeiGene, Roche, Jansen, and GSK. Mateos disclosed ties with AbbVie, Amgen, Bristol-Myers Squibb, GSK, Kite, Johnson & Johnson, Oncopeptides, Pfizer, Regeneron, Roche, and Sanofi.

A version of this article first appeared on Medscape.com.

RIO DE JANEIRO — The addition of daratumumab to lenalidomide maintenance therapy following autologous stem cell transplant (ASCT) significantly improves rates of achieving minimal residual disease (MRD) negativity and progression-free survival (PFS) among patients newly diagnosed with multiple myeloma (MM), new research showed.

“To date, no randomized trial has directly compared daratumumab-based maintenance therapy vs standard of care lenalidomide maintenance, which is the focus of our trial,” said first author Ashraf Z. Badros, MD, a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, in presenting the findings at the International Myeloma Society (IMS) 2024.

“These results support the addition of daratumumab not only to induction/consolidation but also to standard of care lenalidomide maintenance for these patients,” he said of the study, which was published concurrently in the journal Blood.

Despite ongoing advancements in regimens for induction, consolidation, and maintenance posttransplant, most patients with MM eventually relapse, driving continuing efforts to optimize treatment strategies and improve long-term outcomes.

While daratumumab, an anti-CD38 monoclonal antibody, is approved in induction and consolidation with ASCT for patients with newly diagnosed MM, the authors sought to investigate the potential benefits of adding it to the standard-of-care therapy lenalidomide in maintenance therapy.

For the phase 3 AURIGA trial, they recruited 200 patients with newly diagnosed MM within 12 months of induction therapy and 6 months of ASCT.

The patients, who were all anti-CD38 naive, received at least four induction cycles, had at least a very good partial response, and were MRD positive following ASCT.

They were randomized 1:1 to receive 28-day lenalidomide maintenance cycles either with (n = 99) or without (n = 101) subcutaneous daratumumab for at least 36 cycles or until disease progression, unacceptable toxicity, or withdrawal.

The patients had similar baseline demographic characteristics; their median age was about 62 years, and 25.3% in the daratumumab and 23.5% in the no-daratumumab group had ISS stage III disease. At the time of diagnosis, 23.9% and 16.9%, respectively, had high cytogenic risk.

Overall, patients received a median of five induction cycles prior to entering the study.

For the primary endpoint, the rate of conversion from MRD positive to MRD negative (at a sensitivity of 10-5 using next-generation sequencing) by 12 months was significantly higher in the daratumumab group than in the lenalidomide-only group, at 50.5% vs 18.8% (odds ratio [OR], 4.51; P < .0001).

A similar benefit with the daratumumab group was observed across all clinically relevant subgroups, including patients with high-risk disease.

The MRD-negative conversion rate was similar at the 10-6 threshold (23.2% vs 5%; OR, 5.97; P = .0002).

At a median follow-up of 32.3 months, the overall rates of MRD negativity were 60.6% and 27.7%, with and without daratumumab, respectively (OR, 4.12; P < .0001)

The achievement of complete response or better also was significantly greater with daratumumab (75.8% vs 61.4%; OR, 2.00; P = .0255).

Likewise, PFS favored daratumumab (hazard ratio, 0.53), and the estimated 30-month PFS rates were 82.7% and 66.4%, respectively.

The daratumumab group received more maintenance cycles than the lenalidomide-only group (median of 33 vs 21.5), and it had higher rates of completion of 12 cycles (88.5% vs 78.6%). Dr. Badros noted that the main reason for discontinuation of therapy in the no-daratumumab arm was disease progression.

Consistent with previous studies, daratumumab was associated with more grade 3/4 treatment-emergent adverse events (TEAEs), occurring in 74.0% patients vs 67.3% patients not receiving daratumumab, including infections (18.8% vs 13.3%), cytopenia (54.2% vs 46.9%), and neutropenia (46.9% vs 41.8%). Dr. Badros noted the significantly longer time of treatment in the daratumumab arm (30 months vs 20 months).

Serious TEAEs occurred in 30.2% daratumumab patients and 22.4% no-daratumumab patients, and fatal TEAEs occurred in 2.1% and 1.0% patients, respectively.

“Overall, there were no new safety concerns for daratumumab,” he said.

The authors noted that the requirement that patients be anti-CD38 naive was partially because of “the D-VRd [daratumumab combined with bortezomib, lenalidomide, and dexamethasone] regimen gaining popularity and increased utilization in the myeloma community for transplant-eligible patients with NDMM, even before the publication of the long-term results of the randomized GRIFFIN and PERSEUS studies.”

A key question, remarked Joseph Mikhael, MD, who is chief medical officer of the International Myeloma Foundation, from the audience, is how applicable the findings are in the modern environment, where most patients now have indeed had prior anti-CD38 treatment.

In response, Dr. Badros explained that “I think this is an important study because it is probably one of the few studies that separates the impact of daratumumab-lenalidomide without prior daratumumab use.”

Dr. Badros noted that results from the PERSEUS trial, of D-VRd, show MRD-positive to MRD-negative conversion rates that are similar to the current trial; “therefore, I really don’t think that using daratumumab up front will prevent using it as maintenance,” he said. “If anything, it actually improves outcomes.”

The findings from continuous treatment “are an important reminder that high-risk patients do not do well if you stop treatment,” he said.

Further commenting on the research at the meeting, María-Victoria Mateos, MD, PhD, an associate professor of medicine at the University of Salamanca in Spain, noted that “the unmet need in maintenance is to upgrade the quality of the response and to increase the conversion of MRD-positivity to MRD negative in order to delay the progression of the disease and prolong the overall survival.”

Regarding the AURIGA trial, “this is very interesting data about the role of daratumumab-lenalidomide maintenance in patients who are MRD positive after autologous stem cell transplantation.”

“What is more important is we are progressing in response-adaptive therapy, and we are generating very useful information to possibly make the majority of patients become MRD negative.

“Developing early endpoints as surrogate markers for long-term outcomes and overall survival is critically important,” she added. “Otherwise, trials may continue for more than 15 years.”

The study was sponsored by Janssen Biotech. Dr. Badros reported relationships with Bristol-Myers Squibb, BeiGene, Roche, Jansen, and GSK. Mateos disclosed ties with AbbVie, Amgen, Bristol-Myers Squibb, GSK, Kite, Johnson & Johnson, Oncopeptides, Pfizer, Regeneron, Roche, and Sanofi.

A version of this article first appeared on Medscape.com.

RIO DE JANEIRO — The addition of daratumumab to lenalidomide maintenance therapy following autologous stem cell transplant (ASCT) significantly improves rates of achieving minimal residual disease (MRD) negativity and progression-free survival (PFS) among patients newly diagnosed with multiple myeloma (MM), new research showed.

“To date, no randomized trial has directly compared daratumumab-based maintenance therapy vs standard of care lenalidomide maintenance, which is the focus of our trial,” said first author Ashraf Z. Badros, MD, a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical Center, Baltimore, in presenting the findings at the International Myeloma Society (IMS) 2024.

“These results support the addition of daratumumab not only to induction/consolidation but also to standard of care lenalidomide maintenance for these patients,” he said of the study, which was published concurrently in the journal Blood.

Despite ongoing advancements in regimens for induction, consolidation, and maintenance posttransplant, most patients with MM eventually relapse, driving continuing efforts to optimize treatment strategies and improve long-term outcomes.

While daratumumab, an anti-CD38 monoclonal antibody, is approved in induction and consolidation with ASCT for patients with newly diagnosed MM, the authors sought to investigate the potential benefits of adding it to the standard-of-care therapy lenalidomide in maintenance therapy.

For the phase 3 AURIGA trial, they recruited 200 patients with newly diagnosed MM within 12 months of induction therapy and 6 months of ASCT.

The patients, who were all anti-CD38 naive, received at least four induction cycles, had at least a very good partial response, and were MRD positive following ASCT.

They were randomized 1:1 to receive 28-day lenalidomide maintenance cycles either with (n = 99) or without (n = 101) subcutaneous daratumumab for at least 36 cycles or until disease progression, unacceptable toxicity, or withdrawal.

The patients had similar baseline demographic characteristics; their median age was about 62 years, and 25.3% in the daratumumab and 23.5% in the no-daratumumab group had ISS stage III disease. At the time of diagnosis, 23.9% and 16.9%, respectively, had high cytogenic risk.

Overall, patients received a median of five induction cycles prior to entering the study.

For the primary endpoint, the rate of conversion from MRD positive to MRD negative (at a sensitivity of 10-5 using next-generation sequencing) by 12 months was significantly higher in the daratumumab group than in the lenalidomide-only group, at 50.5% vs 18.8% (odds ratio [OR], 4.51; P < .0001).

A similar benefit with the daratumumab group was observed across all clinically relevant subgroups, including patients with high-risk disease.

The MRD-negative conversion rate was similar at the 10-6 threshold (23.2% vs 5%; OR, 5.97; P = .0002).

At a median follow-up of 32.3 months, the overall rates of MRD negativity were 60.6% and 27.7%, with and without daratumumab, respectively (OR, 4.12; P < .0001)

The achievement of complete response or better also was significantly greater with daratumumab (75.8% vs 61.4%; OR, 2.00; P = .0255).

Likewise, PFS favored daratumumab (hazard ratio, 0.53), and the estimated 30-month PFS rates were 82.7% and 66.4%, respectively.

The daratumumab group received more maintenance cycles than the lenalidomide-only group (median of 33 vs 21.5), and it had higher rates of completion of 12 cycles (88.5% vs 78.6%). Dr. Badros noted that the main reason for discontinuation of therapy in the no-daratumumab arm was disease progression.

Consistent with previous studies, daratumumab was associated with more grade 3/4 treatment-emergent adverse events (TEAEs), occurring in 74.0% patients vs 67.3% patients not receiving daratumumab, including infections (18.8% vs 13.3%), cytopenia (54.2% vs 46.9%), and neutropenia (46.9% vs 41.8%). Dr. Badros noted the significantly longer time of treatment in the daratumumab arm (30 months vs 20 months).

Serious TEAEs occurred in 30.2% daratumumab patients and 22.4% no-daratumumab patients, and fatal TEAEs occurred in 2.1% and 1.0% patients, respectively.

“Overall, there were no new safety concerns for daratumumab,” he said.

The authors noted that the requirement that patients be anti-CD38 naive was partially because of “the D-VRd [daratumumab combined with bortezomib, lenalidomide, and dexamethasone] regimen gaining popularity and increased utilization in the myeloma community for transplant-eligible patients with NDMM, even before the publication of the long-term results of the randomized GRIFFIN and PERSEUS studies.”

A key question, remarked Joseph Mikhael, MD, who is chief medical officer of the International Myeloma Foundation, from the audience, is how applicable the findings are in the modern environment, where most patients now have indeed had prior anti-CD38 treatment.

In response, Dr. Badros explained that “I think this is an important study because it is probably one of the few studies that separates the impact of daratumumab-lenalidomide without prior daratumumab use.”

Dr. Badros noted that results from the PERSEUS trial, of D-VRd, show MRD-positive to MRD-negative conversion rates that are similar to the current trial; “therefore, I really don’t think that using daratumumab up front will prevent using it as maintenance,” he said. “If anything, it actually improves outcomes.”

The findings from continuous treatment “are an important reminder that high-risk patients do not do well if you stop treatment,” he said.

Further commenting on the research at the meeting, María-Victoria Mateos, MD, PhD, an associate professor of medicine at the University of Salamanca in Spain, noted that “the unmet need in maintenance is to upgrade the quality of the response and to increase the conversion of MRD-positivity to MRD negative in order to delay the progression of the disease and prolong the overall survival.”

Regarding the AURIGA trial, “this is very interesting data about the role of daratumumab-lenalidomide maintenance in patients who are MRD positive after autologous stem cell transplantation.”

“What is more important is we are progressing in response-adaptive therapy, and we are generating very useful information to possibly make the majority of patients become MRD negative.

“Developing early endpoints as surrogate markers for long-term outcomes and overall survival is critically important,” she added. “Otherwise, trials may continue for more than 15 years.”

The study was sponsored by Janssen Biotech. Dr. Badros reported relationships with Bristol-Myers Squibb, BeiGene, Roche, Jansen, and GSK. Mateos disclosed ties with AbbVie, Amgen, Bristol-Myers Squibb, GSK, Kite, Johnson & Johnson, Oncopeptides, Pfizer, Regeneron, Roche, and Sanofi.

A version of this article first appeared on Medscape.com.

Ferritin is the parameter most often used in primary care to diagnose iron deficiency. The cutoff value of ferritin can affect the number of cases diagnosed, however. A study published in JAMA Network Open  investigated how different cutoff values affect the diagnosis of iron deficiency.

The study, which included 255,351 adult primary care patients in Switzerland, showed that ferritin cutoff values of 15, 30, and 45 ng/mL were associated with incidences of iron deficiency diagnoses of 10.9, 29.9, and 48.3 cases per 1000 patient-years, respectively. In other words, as the cutoff value increases, the frequency of diagnosis also increases.

“It is a study to take into account, especially because of the number of patients it includes, and it can guide primary care clinical practice. As expected, as the cutoff point increases with respect to ferritin values, the incidence percentages of both iron deficiency and iron-deficiency anemia also increase,” Miguel Turégano-Yedro, MD, a family physician at the Casar de Cáceres Health Center in Spain, and coordinator of the Hematology Working Group of the Spanish Society of Primary Care Physicians, told this news organization. Ferritin is the most sensitive parameter for diagnosing iron deficiency and iron-deficiency anemia, he added. “When it is necessary to supplement a patient with iron, other parameters are taken into account, such as hemoglobin, to see if there is anemia.”
 

Ferritin Level

The ferritin level associated with iron deficiency in primary care is usually 15 ng/mL, said Dr. Turégano-Yedro. “If we assess patients with a ferritin level of 15 or less than 15, then we know that many cases will be symptomatic (with fatigue, tiredness, or lack of appetite) and, therefore, will need iron treatment. But if the ferritin cutoff value is increased to 30 ng/mL or 45 ng/mL, the incidence will be higher, although in many cases they will be asymptomatic and iron supplementation will not be necessary.”

He also pointed out that he does not consider it necessary to raise the cutoff to 45 ng/mL; however, “establishing the cutoff at 30 ng/mL, in a certain population at risk of iron deficiency or iron-deficiency anemia, may be interesting, for example in women of childbearing age, women with very heavy menstruation, children, frail elderly, people with gastrointestinal bleeding, or those who engage in physical exercise.”

Iron deficiency must be distinguished from anemia. “If the ferritin is below 15 ng/mL, there is iron deficiency, which may or may not be accompanied by symptoms, although usually most patients will have symptoms. Normally, to diagnose a patient with iron-deficiency anemia, on the one hand, they must have low hemoglobin, which indicates anemia, and on the other hand, low ferritin, which indicates iron deficiency.” Taking these parameters into account, the study does have a weakness. “It is striking that a percentage of patients in the study requested ferritin analysis without including hemoglobin, when hemoglobin is part of the basic analysis performed in Spain,” said Dr. Turégano-Yedro.
 

When to Supplement

The study highlights the incidence of nonanemic iron deficiency diagnoses associated with the choice of ferritin cutoff value. However, as Dr. Turégano-Yedro explained, the percentage of patients who have iron deficiency but do not have anemia is not very relevant. “In the case of family physicians in Spain, it is not usually taken into account, because if a patient has iron deficiency with or without anemia and is symptomatic, they should be given iron supplements.”

What if they do not have a deficiency but do have anemia? “In principle, iron supplementation is not necessary, because that anemia may be due to chronic disorders or it may be hemolytic anemia, so the case should be studied,” Dr. Turégano-Yedro concluded.

This story was translated from Univadis Spain, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Ferritin is the parameter most often used in primary care to diagnose iron deficiency. The cutoff value of ferritin can affect the number of cases diagnosed, however. A study published in JAMA Network Open  investigated how different cutoff values affect the diagnosis of iron deficiency.

The study, which included 255,351 adult primary care patients in Switzerland, showed that ferritin cutoff values of 15, 30, and 45 ng/mL were associated with incidences of iron deficiency diagnoses of 10.9, 29.9, and 48.3 cases per 1000 patient-years, respectively. In other words, as the cutoff value increases, the frequency of diagnosis also increases.

“It is a study to take into account, especially because of the number of patients it includes, and it can guide primary care clinical practice. As expected, as the cutoff point increases with respect to ferritin values, the incidence percentages of both iron deficiency and iron-deficiency anemia also increase,” Miguel Turégano-Yedro, MD, a family physician at the Casar de Cáceres Health Center in Spain, and coordinator of the Hematology Working Group of the Spanish Society of Primary Care Physicians, told this news organization. Ferritin is the most sensitive parameter for diagnosing iron deficiency and iron-deficiency anemia, he added. “When it is necessary to supplement a patient with iron, other parameters are taken into account, such as hemoglobin, to see if there is anemia.”
 

Ferritin Level

The ferritin level associated with iron deficiency in primary care is usually 15 ng/mL, said Dr. Turégano-Yedro. “If we assess patients with a ferritin level of 15 or less than 15, then we know that many cases will be symptomatic (with fatigue, tiredness, or lack of appetite) and, therefore, will need iron treatment. But if the ferritin cutoff value is increased to 30 ng/mL or 45 ng/mL, the incidence will be higher, although in many cases they will be asymptomatic and iron supplementation will not be necessary.”

He also pointed out that he does not consider it necessary to raise the cutoff to 45 ng/mL; however, “establishing the cutoff at 30 ng/mL, in a certain population at risk of iron deficiency or iron-deficiency anemia, may be interesting, for example in women of childbearing age, women with very heavy menstruation, children, frail elderly, people with gastrointestinal bleeding, or those who engage in physical exercise.”

Iron deficiency must be distinguished from anemia. “If the ferritin is below 15 ng/mL, there is iron deficiency, which may or may not be accompanied by symptoms, although usually most patients will have symptoms. Normally, to diagnose a patient with iron-deficiency anemia, on the one hand, they must have low hemoglobin, which indicates anemia, and on the other hand, low ferritin, which indicates iron deficiency.” Taking these parameters into account, the study does have a weakness. “It is striking that a percentage of patients in the study requested ferritin analysis without including hemoglobin, when hemoglobin is part of the basic analysis performed in Spain,” said Dr. Turégano-Yedro.
 

When to Supplement

The study highlights the incidence of nonanemic iron deficiency diagnoses associated with the choice of ferritin cutoff value. However, as Dr. Turégano-Yedro explained, the percentage of patients who have iron deficiency but do not have anemia is not very relevant. “In the case of family physicians in Spain, it is not usually taken into account, because if a patient has iron deficiency with or without anemia and is symptomatic, they should be given iron supplements.”

What if they do not have a deficiency but do have anemia? “In principle, iron supplementation is not necessary, because that anemia may be due to chronic disorders or it may be hemolytic anemia, so the case should be studied,” Dr. Turégano-Yedro concluded.

This story was translated from Univadis Spain, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Ferritin is the parameter most often used in primary care to diagnose iron deficiency. The cutoff value of ferritin can affect the number of cases diagnosed, however. A study published in JAMA Network Open  investigated how different cutoff values affect the diagnosis of iron deficiency.

The study, which included 255,351 adult primary care patients in Switzerland, showed that ferritin cutoff values of 15, 30, and 45 ng/mL were associated with incidences of iron deficiency diagnoses of 10.9, 29.9, and 48.3 cases per 1000 patient-years, respectively. In other words, as the cutoff value increases, the frequency of diagnosis also increases.

“It is a study to take into account, especially because of the number of patients it includes, and it can guide primary care clinical practice. As expected, as the cutoff point increases with respect to ferritin values, the incidence percentages of both iron deficiency and iron-deficiency anemia also increase,” Miguel Turégano-Yedro, MD, a family physician at the Casar de Cáceres Health Center in Spain, and coordinator of the Hematology Working Group of the Spanish Society of Primary Care Physicians, told this news organization. Ferritin is the most sensitive parameter for diagnosing iron deficiency and iron-deficiency anemia, he added. “When it is necessary to supplement a patient with iron, other parameters are taken into account, such as hemoglobin, to see if there is anemia.”
 

Ferritin Level

The ferritin level associated with iron deficiency in primary care is usually 15 ng/mL, said Dr. Turégano-Yedro. “If we assess patients with a ferritin level of 15 or less than 15, then we know that many cases will be symptomatic (with fatigue, tiredness, or lack of appetite) and, therefore, will need iron treatment. But if the ferritin cutoff value is increased to 30 ng/mL or 45 ng/mL, the incidence will be higher, although in many cases they will be asymptomatic and iron supplementation will not be necessary.”

He also pointed out that he does not consider it necessary to raise the cutoff to 45 ng/mL; however, “establishing the cutoff at 30 ng/mL, in a certain population at risk of iron deficiency or iron-deficiency anemia, may be interesting, for example in women of childbearing age, women with very heavy menstruation, children, frail elderly, people with gastrointestinal bleeding, or those who engage in physical exercise.”

Iron deficiency must be distinguished from anemia. “If the ferritin is below 15 ng/mL, there is iron deficiency, which may or may not be accompanied by symptoms, although usually most patients will have symptoms. Normally, to diagnose a patient with iron-deficiency anemia, on the one hand, they must have low hemoglobin, which indicates anemia, and on the other hand, low ferritin, which indicates iron deficiency.” Taking these parameters into account, the study does have a weakness. “It is striking that a percentage of patients in the study requested ferritin analysis without including hemoglobin, when hemoglobin is part of the basic analysis performed in Spain,” said Dr. Turégano-Yedro.
 

When to Supplement

The study highlights the incidence of nonanemic iron deficiency diagnoses associated with the choice of ferritin cutoff value. However, as Dr. Turégano-Yedro explained, the percentage of patients who have iron deficiency but do not have anemia is not very relevant. “In the case of family physicians in Spain, it is not usually taken into account, because if a patient has iron deficiency with or without anemia and is symptomatic, they should be given iron supplements.”

What if they do not have a deficiency but do have anemia? “In principle, iron supplementation is not necessary, because that anemia may be due to chronic disorders or it may be hemolytic anemia, so the case should be studied,” Dr. Turégano-Yedro concluded.

This story was translated from Univadis Spain, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.