SAVANNAH, GEORGIA — Teamwork and transdisciplinary collaboration create an effective system of care for amyotrophic lateral sclerosis (ALS), ensuring improved health both for patients and clinicians alike, said one expert.

In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”

Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.

“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.” 
 

Multidisciplinary vs Interdisciplinary

Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.

In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.

The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.

Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.

Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.

She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
 

Better Together

A recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.

“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.

Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.

Howard and Schellenberg reported no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Teamwork and transdisciplinary collaboration create an effective system of care for amyotrophic lateral sclerosis (ALS), ensuring improved health both for patients and clinicians alike, said one expert.

In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”

Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.

“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.” 
 

Multidisciplinary vs Interdisciplinary

Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.

In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.

The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.

Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.

Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.

She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
 

Better Together

A recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.

“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.

Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.

Howard and Schellenberg reported no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — Teamwork and transdisciplinary collaboration create an effective system of care for amyotrophic lateral sclerosis (ALS), ensuring improved health both for patients and clinicians alike, said one expert.

In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”

Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.

“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.” 
 

Multidisciplinary vs Interdisciplinary

Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.

In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.

The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.

Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.

Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.

She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
 

Better Together

A recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.

“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.

Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.

Howard and Schellenberg reported no disclosures.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — A digital tool to help neurologists assess steroid toxicity in patients with myasthenia gravis (MG) demonstrated sensitivity in distinguishing between different doses and durations of steroid exposure in a retrospective, real-world study.

The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.

“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.

The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Rapid Evidence of Toxicity

The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.

The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.

Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.

As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.

The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
 

Clinical Application

The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.

In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.

“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.

Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.

The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.

However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.

She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.

“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”

For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.

Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — A digital tool to help neurologists assess steroid toxicity in patients with myasthenia gravis (MG) demonstrated sensitivity in distinguishing between different doses and durations of steroid exposure in a retrospective, real-world study.

The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.

“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.

The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Rapid Evidence of Toxicity

The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.

The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.

Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.

As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.

The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
 

Clinical Application

The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.

In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.

“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.

Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.

The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.

However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.

She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.

“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”

For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.

Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
 

A version of this article appeared on Medscape.com.

SAVANNAH, GEORGIA — A digital tool to help neurologists assess steroid toxicity in patients with myasthenia gravis (MG) demonstrated sensitivity in distinguishing between different doses and durations of steroid exposure in a retrospective, real-world study.

The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.

“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.

The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Rapid Evidence of Toxicity

The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.

The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.

Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.

As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.

The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
 

Clinical Application

The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.

In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.

“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.

Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.

The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.

However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.

She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.

“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”

For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.

Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
 

A version of this article appeared on Medscape.com.

Hot Topics in Primary Care 2024 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. 

• Case Studies in Continuous Glucose Monitoring
• Detection and Diagnosis of Early Symptomatic 
  Alzheimer’s Disease in Primary Care
• Elevating the Importance of Asthma Care in the United States
• Hypercortisolism is More Common Than You Think – 
  Here’s How to Find It
• Improving COPD Management at Transitions of Care
• Improving Patient-Centric COPD Management 
• The Role of Finerenone in Optimizing Cardiovascular-
  Kidney-Metabolic Health: Everything PCPs Should Know
• What Primary Care Clinicians Need to Know About Once-Weekly Insulins

This supplement offers the opportunity to earn a total of 3 continuing medical education (CME) credits. Credit is awarded for the successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read the 2024 Hot Topics in Primary Care

Hot Topics in Primary Care 2024 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. 

• Case Studies in Continuous Glucose Monitoring
• Detection and Diagnosis of Early Symptomatic 
  Alzheimer’s Disease in Primary Care
• Elevating the Importance of Asthma Care in the United States
• Hypercortisolism is More Common Than You Think – 
  Here’s How to Find It
• Improving COPD Management at Transitions of Care
• Improving Patient-Centric COPD Management 
• The Role of Finerenone in Optimizing Cardiovascular-
  Kidney-Metabolic Health: Everything PCPs Should Know
• What Primary Care Clinicians Need to Know About Once-Weekly Insulins

This supplement offers the opportunity to earn a total of 3 continuing medical education (CME) credits. Credit is awarded for the successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read the 2024 Hot Topics in Primary Care

Hot Topics in Primary Care 2024 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. 

• Case Studies in Continuous Glucose Monitoring
• Detection and Diagnosis of Early Symptomatic 
  Alzheimer’s Disease in Primary Care
• Elevating the Importance of Asthma Care in the United States
• Hypercortisolism is More Common Than You Think – 
  Here’s How to Find It
• Improving COPD Management at Transitions of Care
• Improving Patient-Centric COPD Management 
• The Role of Finerenone in Optimizing Cardiovascular-
  Kidney-Metabolic Health: Everything PCPs Should Know
• What Primary Care Clinicians Need to Know About Once-Weekly Insulins

This supplement offers the opportunity to earn a total of 3 continuing medical education (CME) credits. Credit is awarded for the successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read the 2024 Hot Topics in Primary Care

TOPLINE: 

High-intensity exercise suppresses ghrelin levels more than moderate-intensity exercise, leading to a greater reduction in hunger. This effect may be more pronounced in women than in men.

METHODOLOGY:

• Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
• To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
• Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2_peak) test to determine the exercise intensity.
• Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2_peak).
• Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.

TAKEAWAY:

• Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
• Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
• Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
• Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).

IN PRACTICE:

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

SOURCE:

This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.

LIMITATIONS: 

The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.

DISCLOSURES:

The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
 

This article was created 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.

TOPLINE: 

High-intensity exercise suppresses ghrelin levels more than moderate-intensity exercise, leading to a greater reduction in hunger. This effect may be more pronounced in women than in men.

METHODOLOGY:

• Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
• To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
• Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2_peak) test to determine the exercise intensity.
• Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2_peak).
• Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.

TAKEAWAY:

• Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
• Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
• Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
• Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).

IN PRACTICE:

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

SOURCE:

This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.

LIMITATIONS: 

The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.

DISCLOSURES:

The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
 

This article was created 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.

TOPLINE: 

High-intensity exercise suppresses ghrelin levels more than moderate-intensity exercise, leading to a greater reduction in hunger. This effect may be more pronounced in women than in men.

METHODOLOGY:

• Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
• To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
• Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2_peak) test to determine the exercise intensity.
• Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2_peak).
• Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.

TAKEAWAY:

• Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
• Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
• Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
• Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).

IN PRACTICE:

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

SOURCE:

This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.

LIMITATIONS: 

The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.

DISCLOSURES:

The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
 

This article was created 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.

As primary care doctors, we diagnosis and treat many patients with osteoarthritis. In fact, according to World Health Organization statistics, approximately 528 million people around the world suffer from some form of this type of arthritis. With the aging of the population and the obesity epidemic, the rate of osteoarthritis has increased 113% since 1990 and is predicted to continue to rise.

While the knee is the most commonly affected joint, osteoarthritis also frequently affects the hands and hips. The American Academy of Orthopaedic Surgeons issued guidelines concerning the management of osteoarthritis of the hip. The clinical guidelines are aimed at orthopedists, but it is important for primary care doctors be aware of them as well since we are the physicians who usually diagnose the disease, manage it in its early stages, and follow the patients with and after the orthopedist has undertaken any procedures.

Castle Connolly

While the complete set of guidelines is 80 pages long, strong recommendations have been made that everyone should be aware of. The role of non-steroidal anti-inflammatory drugs has been reconfirmed as a modality to improve pain and function. A recommendation against using intra-articular hyaluronic acid in the hip was made as the evidence shows it did not improve pain or function better than placebo. Conversely, intra-articular corticosteroids were shown to improve pain and function in the short-term and many primary care doctors provide this treatment in their practice.

These guidelines do a great job covering the totality of management of osteoarthritis of the hip, from conservation management to surgical and post-surgical treatments. Patients often come to us with their questions so not only is it important to know the evidence for what we do in our practices, we need to know what our orthopedic colleagues are doing. We will be the ones asked to do the pre-operative evaluations on these patients, so we need to understand the procedure and its risks. We will also manage these patients post-operatively and need to be aware of what the evidence shows.

Opioid use is also covered in the guidelines: they recommend against the use of opioids to control pain in these patients. In the age of the opioid epidemic, it is a good reminder to be cautious with these meds. It is also a good time to stress smoking cessation with patients.

The guidelines discuss adverse outcomes in patients with diabetes and/or obesity. As primary care physicians, we need to be aware of those risks and be sure our patients are medically optimized before signing that pre-operative form.

A new feature of these guidelines is a discussion on social detriments to health. This is important for many diseases that we treat and we often don’t realize the impact they can have on a patient’s health and recovery. Even if we know a patient would benefit from physical therapy, it doesn’t help them if the patient has no way to get to the appointment. Some patients have copays for every physical therapy session and just can’t afford it. Knowing what the patient needs medically is not enough. We need to understand how they can access that care. Some patients have no one to help them after hip surgery and may avoid doing it for that reason. As primary care doctors, we should be helping our patients access the care they need.

We need to be able to say that a procedure needs to be delayed in the face of poorly controlled disease, such as diabetes. As the rates of osteoarthritis continue to rise, we need to understand that it is not an inevitable age-based occurrence in a patient’s life but rather an inflammatory disease that causes great pain and dysfunction. Utilizing these guidelines and working with our orthopedic colleagues can help patients decrease pain, improve functioning, and enjoy life again.
 

Dr. Girgis practices family medicine in South River, New Jersey, and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, New Jersey. She was paid by Pfizer as a consultant on Paxlovid, paid by GlaxoSmithKline as a consultant for the Shingrix vaccine, and is the editor in chief of Physician’s Weekly.

As primary care doctors, we diagnosis and treat many patients with osteoarthritis. In fact, according to World Health Organization statistics, approximately 528 million people around the world suffer from some form of this type of arthritis. With the aging of the population and the obesity epidemic, the rate of osteoarthritis has increased 113% since 1990 and is predicted to continue to rise.

While the knee is the most commonly affected joint, osteoarthritis also frequently affects the hands and hips. The American Academy of Orthopaedic Surgeons issued guidelines concerning the management of osteoarthritis of the hip. The clinical guidelines are aimed at orthopedists, but it is important for primary care doctors be aware of them as well since we are the physicians who usually diagnose the disease, manage it in its early stages, and follow the patients with and after the orthopedist has undertaken any procedures.

Castle Connolly

While the complete set of guidelines is 80 pages long, strong recommendations have been made that everyone should be aware of. The role of non-steroidal anti-inflammatory drugs has been reconfirmed as a modality to improve pain and function. A recommendation against using intra-articular hyaluronic acid in the hip was made as the evidence shows it did not improve pain or function better than placebo. Conversely, intra-articular corticosteroids were shown to improve pain and function in the short-term and many primary care doctors provide this treatment in their practice.

These guidelines do a great job covering the totality of management of osteoarthritis of the hip, from conservation management to surgical and post-surgical treatments. Patients often come to us with their questions so not only is it important to know the evidence for what we do in our practices, we need to know what our orthopedic colleagues are doing. We will be the ones asked to do the pre-operative evaluations on these patients, so we need to understand the procedure and its risks. We will also manage these patients post-operatively and need to be aware of what the evidence shows.

Opioid use is also covered in the guidelines: they recommend against the use of opioids to control pain in these patients. In the age of the opioid epidemic, it is a good reminder to be cautious with these meds. It is also a good time to stress smoking cessation with patients.

The guidelines discuss adverse outcomes in patients with diabetes and/or obesity. As primary care physicians, we need to be aware of those risks and be sure our patients are medically optimized before signing that pre-operative form.

A new feature of these guidelines is a discussion on social detriments to health. This is important for many diseases that we treat and we often don’t realize the impact they can have on a patient’s health and recovery. Even if we know a patient would benefit from physical therapy, it doesn’t help them if the patient has no way to get to the appointment. Some patients have copays for every physical therapy session and just can’t afford it. Knowing what the patient needs medically is not enough. We need to understand how they can access that care. Some patients have no one to help them after hip surgery and may avoid doing it for that reason. As primary care doctors, we should be helping our patients access the care they need.

We need to be able to say that a procedure needs to be delayed in the face of poorly controlled disease, such as diabetes. As the rates of osteoarthritis continue to rise, we need to understand that it is not an inevitable age-based occurrence in a patient’s life but rather an inflammatory disease that causes great pain and dysfunction. Utilizing these guidelines and working with our orthopedic colleagues can help patients decrease pain, improve functioning, and enjoy life again.
 

Dr. Girgis practices family medicine in South River, New Jersey, and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, New Jersey. She was paid by Pfizer as a consultant on Paxlovid, paid by GlaxoSmithKline as a consultant for the Shingrix vaccine, and is the editor in chief of Physician’s Weekly.

As primary care doctors, we diagnosis and treat many patients with osteoarthritis. In fact, according to World Health Organization statistics, approximately 528 million people around the world suffer from some form of this type of arthritis. With the aging of the population and the obesity epidemic, the rate of osteoarthritis has increased 113% since 1990 and is predicted to continue to rise.

While the knee is the most commonly affected joint, osteoarthritis also frequently affects the hands and hips. The American Academy of Orthopaedic Surgeons issued guidelines concerning the management of osteoarthritis of the hip. The clinical guidelines are aimed at orthopedists, but it is important for primary care doctors be aware of them as well since we are the physicians who usually diagnose the disease, manage it in its early stages, and follow the patients with and after the orthopedist has undertaken any procedures.

Castle Connolly

While the complete set of guidelines is 80 pages long, strong recommendations have been made that everyone should be aware of. The role of non-steroidal anti-inflammatory drugs has been reconfirmed as a modality to improve pain and function. A recommendation against using intra-articular hyaluronic acid in the hip was made as the evidence shows it did not improve pain or function better than placebo. Conversely, intra-articular corticosteroids were shown to improve pain and function in the short-term and many primary care doctors provide this treatment in their practice.

These guidelines do a great job covering the totality of management of osteoarthritis of the hip, from conservation management to surgical and post-surgical treatments. Patients often come to us with their questions so not only is it important to know the evidence for what we do in our practices, we need to know what our orthopedic colleagues are doing. We will be the ones asked to do the pre-operative evaluations on these patients, so we need to understand the procedure and its risks. We will also manage these patients post-operatively and need to be aware of what the evidence shows.

Opioid use is also covered in the guidelines: they recommend against the use of opioids to control pain in these patients. In the age of the opioid epidemic, it is a good reminder to be cautious with these meds. It is also a good time to stress smoking cessation with patients.

The guidelines discuss adverse outcomes in patients with diabetes and/or obesity. As primary care physicians, we need to be aware of those risks and be sure our patients are medically optimized before signing that pre-operative form.

A new feature of these guidelines is a discussion on social detriments to health. This is important for many diseases that we treat and we often don’t realize the impact they can have on a patient’s health and recovery. Even if we know a patient would benefit from physical therapy, it doesn’t help them if the patient has no way to get to the appointment. Some patients have copays for every physical therapy session and just can’t afford it. Knowing what the patient needs medically is not enough. We need to understand how they can access that care. Some patients have no one to help them after hip surgery and may avoid doing it for that reason. As primary care doctors, we should be helping our patients access the care they need.

We need to be able to say that a procedure needs to be delayed in the face of poorly controlled disease, such as diabetes. As the rates of osteoarthritis continue to rise, we need to understand that it is not an inevitable age-based occurrence in a patient’s life but rather an inflammatory disease that causes great pain and dysfunction. Utilizing these guidelines and working with our orthopedic colleagues can help patients decrease pain, improve functioning, and enjoy life again.
 

Dr. Girgis practices family medicine in South River, New Jersey, and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, New Jersey. She was paid by Pfizer as a consultant on Paxlovid, paid by GlaxoSmithKline as a consultant for the Shingrix vaccine, and is the editor in chief of Physician’s Weekly.

NEW YORK — When patients with multiple myeloma (MM) relapse following chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsABs), or both, likely salvage options remain that are being overlooked, including a second course of immunotherapy. Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.

“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.

“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.

Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.

A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.

The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.

As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.

Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
 

CELMoDs Active After CAR T-Cell Therapy

Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.

These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.

There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep^®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.

However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.

It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*

Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.

“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.

This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
 

Recycling MM Therapies Deserves Consideration

In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.

Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.

Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.

This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.

“Better T-cell assays may help,” he said.

Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.

*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
 

A version of this article appeared on Medscape.com.

NEW YORK — When patients with multiple myeloma (MM) relapse following chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsABs), or both, likely salvage options remain that are being overlooked, including a second course of immunotherapy. Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.

“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.

“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.

Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.

A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.

The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.

As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.

Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
 

CELMoDs Active After CAR T-Cell Therapy

Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.

These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.

There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep^®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.

However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.

It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*

Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.

“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.

This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
 

Recycling MM Therapies Deserves Consideration

In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.

Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.

Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.

This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.

“Better T-cell assays may help,” he said.

Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.

*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
 

A version of this article appeared on Medscape.com.

NEW YORK — When patients with multiple myeloma (MM) relapse following chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsABs), or both, likely salvage options remain that are being overlooked, including a second course of immunotherapy. Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.

“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.

“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.

Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.

A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.

The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.

As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.

Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
 

CELMoDs Active After CAR T-Cell Therapy

Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.

These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.

There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep^®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.

However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.

It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*

Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.

“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.

This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
 

Recycling MM Therapies Deserves Consideration

In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.

Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.

Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.

This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.

“Better T-cell assays may help,” he said.

Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.

*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
 

A version of this article appeared on Medscape.com.

NEW YORK — In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

NEW YORK — In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

NEW YORK — In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

NEW YORK — In the wake of details about the molecular pathophysiology of Waldenström macroglobulinemia (WM), an expert gave an update on current and expanding options for treatment.

Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.

Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.

While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.

Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
 

Deep Responses in WM Remain Elusive

The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.

On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.

A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.

While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.

“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.

MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
 

CXCR4 Mutations Predict Worse Outcomes

The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.

The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.

The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.

More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.

For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.

“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.

However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.

The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.

The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.

He now thinks of regimens with proteasome inhibitors as third line.

In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
 

T-Cell Engager Data Are Limited

Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.

Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.

“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.

Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
 

A version of this article appeared on Medscape.com.

NEW YORK — In the wake of details about the molecular pathophysiology of Waldenström macroglobulinemia (WM), an expert gave an update on current and expanding options for treatment.

Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.

Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.

While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.

Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
 

Deep Responses in WM Remain Elusive

The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.

On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.

A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.

While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.

“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.

MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
 

CXCR4 Mutations Predict Worse Outcomes

The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.

The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.

The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.

More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.

For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.

“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.

However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.

The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.

The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.

He now thinks of regimens with proteasome inhibitors as third line.

In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
 

T-Cell Engager Data Are Limited

Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.

Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.

“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.

Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
 

A version of this article appeared on Medscape.com.

NEW YORK — In the wake of details about the molecular pathophysiology of Waldenström macroglobulinemia (WM), an expert gave an update on current and expanding options for treatment.

Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.

Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.

While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.

Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
 

Deep Responses in WM Remain Elusive

The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.

On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.

A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.

While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.

“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.

MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
 

CXCR4 Mutations Predict Worse Outcomes

The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.

The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.

The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.

More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.

For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.

“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.

However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.

The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.

The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.

He now thinks of regimens with proteasome inhibitors as third line.

In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
 

T-Cell Engager Data Are Limited

Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.

Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.

“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.

Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
 

A version of this article appeared on Medscape.com.

Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.

Dr. Sophia M. Akhiyat

Dr. Sophia M. Akhiyat

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

J Am Acad Dermatol. 2014 May;70(5):Supplement 1AB118. doi: 10.1016/j.jaad.2014.01.491.

Michels A, Michels N. Am Fam Physician. 2014 Apr 1;89(7):563-568.

Kauzman A et al. J Can Dent Assoc. 2004 Nov;70(10):682-683.

Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.

Dr. Sophia M. Akhiyat

Dr. Sophia M. Akhiyat

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

J Am Acad Dermatol. 2014 May;70(5):Supplement 1AB118. doi: 10.1016/j.jaad.2014.01.491.

Michels A, Michels N. Am Fam Physician. 2014 Apr 1;89(7):563-568.

Kauzman A et al. J Can Dent Assoc. 2004 Nov;70(10):682-683.

Primary adrenal insufficiency (Addison’s disease) results from a dysfunction of the adrenal glands, which may be secondary to autoimmune diseases, genetic conditions, infections, and vasculopathies,or may be drug-induced (e.g. checkpoint inhibitors), among others . In contrast, secondary adrenal insufficiency results from pituitary dysfunction of low adrenocorticotropic hormone (ACTH). The most common cause of primary adrenal insufficiency in developed countries is autoimmune adrenalitis, which accounts for upwards of 90% of cases. Typically, 21-hydroxylase autoantibodies are identified and account for destruction of the adrenal cortex through cell-mediated and humoral immune responses.

Dr. Sophia M. Akhiyat

Dr. Sophia M. Akhiyat

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Florida. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

J Am Acad Dermatol. 2014 May;70(5):Supplement 1AB118. doi: 10.1016/j.jaad.2014.01.491.

Michels A, Michels N. Am Fam Physician. 2014 Apr 1;89(7):563-568.

Kauzman A et al. J Can Dent Assoc. 2004 Nov;70(10):682-683.

A new study provides real-world evidence to support the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for prevention of Alzheimer’s disease.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications. 

“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio. 

The study was published online on October 24 in Alzheimer’s & Dementia.
 

Real-World Data

Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain. 

In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.

Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59). 

Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported. 

The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function. 

For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo. 
 

Promising, but Preliminary 

Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”

“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said. 

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned. 

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said. 

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
 

A version of this article appeared on Medscape.com.

A new study provides real-world evidence to support the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for prevention of Alzheimer’s disease.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications. 

“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio. 

The study was published online on October 24 in Alzheimer’s & Dementia.
 

Real-World Data

Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain. 

In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.

Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59). 

Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported. 

The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function. 

For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo. 
 

Promising, but Preliminary 

Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”

“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said. 

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned. 

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said. 

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
 

A version of this article appeared on Medscape.com.

A new study provides real-world evidence to support the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for prevention of Alzheimer’s disease.

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk for Alzheimer’s disease compared with their peers who were prescribed any of seven other antidiabetic medications, including other types of GLP-1 receptor–targeting medications. 

“These findings support further clinical trials to assess semaglutide’s potential in delaying or preventing Alzheimer’s disease,” wrote the investigators, led by Rong Xu, PhD, with Case Western Reserve School of Medicine, Cleveland, Ohio. 

The study was published online on October 24 in Alzheimer’s & Dementia.
 

Real-World Data

Semaglutide has shown neuroprotective effects in animal models of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. In animal models of Alzheimer’s disease, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain. 

In a real-world analysis, Xu and colleagues used electronic health record data to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic medications, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea, and thiazolidinedione.

Over 3 years, treatment with semaglutide was associated with significantly reduced risk of developing Alzheimer’s disease, most strongly compared with insulin (hazard ratio [HR], 0.33) and most weakly compared with other GLP-1 RAs (HR, 0.59). 

Compared with the other medications, semaglutide was associated with a 40%-70% reduced risk for first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes, with similar reductions seen across obesity status and gender and age groups, the authors reported. 

The findings align with recent evidence suggesting GLP-1 RAs may protect cognitive function. 

For example, as previously reported, in the phase 2b ELAD clinical trial, adults with early-stage Alzheimer’s disease taking the GLP-1 RA liraglutide exhibited slower decline in memory and thinking and experienced less brain atrophy over 12 months compared with placebo. 
 

Promising, but Preliminary 

Reached for comment, Courtney Kloske, PhD, Alzheimer’s Association director of scientific engagement, noted that diabetes is a known risk factor for AD and managing diabetes with drugs such as semaglutide “could benefit brain health simply by managing diabetes.”

“However, we still need large clinical trials in representative populations to determine if semaglutide specifically lowers the risk of Alzheimer’s, so it is too early to recommend it for prevention,” Kloske said. 

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact brain energy use. However, more research is needed to fully understand how these processes might contribute to preventing cognitive decline or Alzheimer’s,” Kloske cautioned. 

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that may address known and potential new aspects of the disease, Kloske said. 

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.
 

A version of this article appeared on Medscape.com.