Lymphoma & Plasma Cell Disorders

Photo by Rhoda Baer

The Hematology/Oncology Pharmacy Association (HOPA) has announced the release of a toolkit intended to help prevent chemotherapy-induced nausea and vomiting (CINV) in cancer patients.

The Time to Talk CINV™ toolkit was designed to facilitate dialogue between patients and their healthcare teams to ensure no patient is needlessly suffering from CINV.

The tools in the kit, which are targeted to both patients and healthcare providers, were created with guidance from patients, caregivers, pharmacists, and nurses.

The entire toolkit is available for free download at TimeToTalkCINV.com.

The toolkit is part of the Time to Talk CINV™ campaign, which is a collaboration between HOPA, Eisai Inc., and Helsinn Therapeutics (US), Inc. (funded by Eisai and Helsinn Therapeutics).

The campaign began in response to results from a survey of cancer patients.

“Our research revealed a vast majority of patients on chemotherapy who experience nausea and vomiting expect to have this side effect, and 95% of these patients said, at some point, chemo-induced nausea and vomiting had an impact on their daily lives,” said Sarah Peters, PharmD, president of HOPA.

“In response to these findings, as well as the finding that healthcare team members are looking for better communication tools, the Time to Talk CINV toolkit was created to facilitate efficient and effective conversations about nausea and vomiting from chemotherapy to ensure that each patient is receiving the right information and effective management approaches.”

The Time to Talk CINV toolkit includes the following resources:

• A list of myths and truths about CINV intended to eliminate common misperceptions
• A checklist of questions patients can ask healthcare providers to better understand CINV
• A chemotherapy side effect tracker, which enables patients to track their experience and report back to their healthcare team
• A communication checklist for the healthcare team outlining best practices for communicating with patients to prevent CINV.

Each tool can be printed or filled out digitally.

Additional information about CINV, including videos and infographics, can be found on the Time to Talk CINV website.

Photo by Rhoda Baer

The Hematology/Oncology Pharmacy Association (HOPA) has announced the release of a toolkit intended to help prevent chemotherapy-induced nausea and vomiting (CINV) in cancer patients.

The Time to Talk CINV™ toolkit was designed to facilitate dialogue between patients and their healthcare teams to ensure no patient is needlessly suffering from CINV.

The tools in the kit, which are targeted to both patients and healthcare providers, were created with guidance from patients, caregivers, pharmacists, and nurses.

The entire toolkit is available for free download at TimeToTalkCINV.com.

The toolkit is part of the Time to Talk CINV™ campaign, which is a collaboration between HOPA, Eisai Inc., and Helsinn Therapeutics (US), Inc. (funded by Eisai and Helsinn Therapeutics).

The campaign began in response to results from a survey of cancer patients.

“Our research revealed a vast majority of patients on chemotherapy who experience nausea and vomiting expect to have this side effect, and 95% of these patients said, at some point, chemo-induced nausea and vomiting had an impact on their daily lives,” said Sarah Peters, PharmD, president of HOPA.

“In response to these findings, as well as the finding that healthcare team members are looking for better communication tools, the Time to Talk CINV toolkit was created to facilitate efficient and effective conversations about nausea and vomiting from chemotherapy to ensure that each patient is receiving the right information and effective management approaches.”

The Time to Talk CINV toolkit includes the following resources:

• A list of myths and truths about CINV intended to eliminate common misperceptions
• A checklist of questions patients can ask healthcare providers to better understand CINV
• A chemotherapy side effect tracker, which enables patients to track their experience and report back to their healthcare team
• A communication checklist for the healthcare team outlining best practices for communicating with patients to prevent CINV.

Each tool can be printed or filled out digitally.

Additional information about CINV, including videos and infographics, can be found on the Time to Talk CINV website.

Photo by Rhoda Baer

The Hematology/Oncology Pharmacy Association (HOPA) has announced the release of a toolkit intended to help prevent chemotherapy-induced nausea and vomiting (CINV) in cancer patients.

The Time to Talk CINV™ toolkit was designed to facilitate dialogue between patients and their healthcare teams to ensure no patient is needlessly suffering from CINV.

The tools in the kit, which are targeted to both patients and healthcare providers, were created with guidance from patients, caregivers, pharmacists, and nurses.

The entire toolkit is available for free download at TimeToTalkCINV.com.

The toolkit is part of the Time to Talk CINV™ campaign, which is a collaboration between HOPA, Eisai Inc., and Helsinn Therapeutics (US), Inc. (funded by Eisai and Helsinn Therapeutics).

The campaign began in response to results from a survey of cancer patients.

“Our research revealed a vast majority of patients on chemotherapy who experience nausea and vomiting expect to have this side effect, and 95% of these patients said, at some point, chemo-induced nausea and vomiting had an impact on their daily lives,” said Sarah Peters, PharmD, president of HOPA.

“In response to these findings, as well as the finding that healthcare team members are looking for better communication tools, the Time to Talk CINV toolkit was created to facilitate efficient and effective conversations about nausea and vomiting from chemotherapy to ensure that each patient is receiving the right information and effective management approaches.”

The Time to Talk CINV toolkit includes the following resources:

• A list of myths and truths about CINV intended to eliminate common misperceptions
• A checklist of questions patients can ask healthcare providers to better understand CINV
• A chemotherapy side effect tracker, which enables patients to track their experience and report back to their healthcare team
• A communication checklist for the healthcare team outlining best practices for communicating with patients to prevent CINV.

Each tool can be printed or filled out digitally.

Additional information about CINV, including videos and infographics, can be found on the Time to Talk CINV website.

Photo courtesy of the FDA

The US Food and Drug Administration (FDA) has issued an update on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said that, as of February 1, it has received 359 reports of BIA-ALCL.

However, the actual number of BIA-ALCL cases remains difficult to determine due to limitations in reporting and a lack of implant sales data.

The FDA also noted that most of the available data suggest BIA-ALCL occurs more frequently in patients who receive implants with textured surfaces rather than smooth surfaces.

The full FDA update includes background information on BIA-ALCL, a summary of medical device reports (MDRs) and the medical literature, as well as recommendations for patient care.

Background and MDRs

The FDA first identified a possible association between ALCL and breast implants in 2011.

The agency now concurs with the World Health Organization’s designation of BIA-ALCL as a rare T-cell lymphoma occurring in patients with breast implants.

The FDA continues to collect and review information about BIA-ALCL. This includes reviewing MDRs and the medical literature, as well as exchanging information with other international regulators and scientific experts.

The FDA said it has received 359 MDRs of BIA-ALCL, including 9 cases in which the patient died.

Information on the implant surface was available for 239 cases, and 203 of these cases involved textured implants.

Information on the implant filling was available in 312 cases. Of these, 186 patients had implants filled with silicone gel, and 126 had implants filled with saline.

Recommendations

The FDA said healthcare providers performing breast implant surgery should provide patients with the manufacturers’ labeling as well as any other educational materials before surgery and discuss with patients the benefits and risks of the different types of implants.

Providers should consider the possibility of BIA-ALCL when a patient presents with late-onset, persistent peri-implant seroma. The FDA noted that, in some cases, patients presented with capsular contracture or masses adjacent to the breast implant.

Patients with suspected BIA-ALCL should be referred to an appropriate specialist.

When testing for BIA-ALCL, providers should collect fresh seroma fluid and representative portions of the capsule and send these samples for pathology tests.

Diagnostic evaluation of patients with suspected BIA-ALCL should include cytological evaluation of seroma fluid with Wright Giemsa stained smears and cell block immunohistochemistry testing for cluster of differentiation and anaplastic lymphoma kinase markers.

When choosing a treatment approach for patients with BIA-ALCL, providers should consider current clinical practice guidelines, such as those from the National Comprehensive Cancer Network (included in the guidelines for T-cell lymphomas) or the Plastic Surgery Foundation.

Finally, providers should report all confirmed cases of BIA-ALCL to the FDA and to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma (ALCL) Etiology and Epidemiology (PROFILE Registry).

Photo courtesy of the FDA

The US Food and Drug Administration (FDA) has issued an update on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said that, as of February 1, it has received 359 reports of BIA-ALCL.

However, the actual number of BIA-ALCL cases remains difficult to determine due to limitations in reporting and a lack of implant sales data.

The FDA also noted that most of the available data suggest BIA-ALCL occurs more frequently in patients who receive implants with textured surfaces rather than smooth surfaces.

The full FDA update includes background information on BIA-ALCL, a summary of medical device reports (MDRs) and the medical literature, as well as recommendations for patient care.

Background and MDRs

The FDA first identified a possible association between ALCL and breast implants in 2011.

The agency now concurs with the World Health Organization’s designation of BIA-ALCL as a rare T-cell lymphoma occurring in patients with breast implants.

The FDA continues to collect and review information about BIA-ALCL. This includes reviewing MDRs and the medical literature, as well as exchanging information with other international regulators and scientific experts.

The FDA said it has received 359 MDRs of BIA-ALCL, including 9 cases in which the patient died.

Information on the implant surface was available for 239 cases, and 203 of these cases involved textured implants.

Information on the implant filling was available in 312 cases. Of these, 186 patients had implants filled with silicone gel, and 126 had implants filled with saline.

Recommendations

The FDA said healthcare providers performing breast implant surgery should provide patients with the manufacturers’ labeling as well as any other educational materials before surgery and discuss with patients the benefits and risks of the different types of implants.

Providers should consider the possibility of BIA-ALCL when a patient presents with late-onset, persistent peri-implant seroma. The FDA noted that, in some cases, patients presented with capsular contracture or masses adjacent to the breast implant.

Patients with suspected BIA-ALCL should be referred to an appropriate specialist.

When testing for BIA-ALCL, providers should collect fresh seroma fluid and representative portions of the capsule and send these samples for pathology tests.

Diagnostic evaluation of patients with suspected BIA-ALCL should include cytological evaluation of seroma fluid with Wright Giemsa stained smears and cell block immunohistochemistry testing for cluster of differentiation and anaplastic lymphoma kinase markers.

When choosing a treatment approach for patients with BIA-ALCL, providers should consider current clinical practice guidelines, such as those from the National Comprehensive Cancer Network (included in the guidelines for T-cell lymphomas) or the Plastic Surgery Foundation.

Finally, providers should report all confirmed cases of BIA-ALCL to the FDA and to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma (ALCL) Etiology and Epidemiology (PROFILE Registry).

Photo courtesy of the FDA

The US Food and Drug Administration (FDA) has issued an update on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said that, as of February 1, it has received 359 reports of BIA-ALCL.

However, the actual number of BIA-ALCL cases remains difficult to determine due to limitations in reporting and a lack of implant sales data.

The FDA also noted that most of the available data suggest BIA-ALCL occurs more frequently in patients who receive implants with textured surfaces rather than smooth surfaces.

The full FDA update includes background information on BIA-ALCL, a summary of medical device reports (MDRs) and the medical literature, as well as recommendations for patient care.

Background and MDRs

The FDA first identified a possible association between ALCL and breast implants in 2011.

The agency now concurs with the World Health Organization’s designation of BIA-ALCL as a rare T-cell lymphoma occurring in patients with breast implants.

The FDA continues to collect and review information about BIA-ALCL. This includes reviewing MDRs and the medical literature, as well as exchanging information with other international regulators and scientific experts.

The FDA said it has received 359 MDRs of BIA-ALCL, including 9 cases in which the patient died.

Information on the implant surface was available for 239 cases, and 203 of these cases involved textured implants.

Information on the implant filling was available in 312 cases. Of these, 186 patients had implants filled with silicone gel, and 126 had implants filled with saline.

Recommendations

The FDA said healthcare providers performing breast implant surgery should provide patients with the manufacturers’ labeling as well as any other educational materials before surgery and discuss with patients the benefits and risks of the different types of implants.

Providers should consider the possibility of BIA-ALCL when a patient presents with late-onset, persistent peri-implant seroma. The FDA noted that, in some cases, patients presented with capsular contracture or masses adjacent to the breast implant.

Patients with suspected BIA-ALCL should be referred to an appropriate specialist.

When testing for BIA-ALCL, providers should collect fresh seroma fluid and representative portions of the capsule and send these samples for pathology tests.

Diagnostic evaluation of patients with suspected BIA-ALCL should include cytological evaluation of seroma fluid with Wright Giemsa stained smears and cell block immunohistochemistry testing for cluster of differentiation and anaplastic lymphoma kinase markers.

When choosing a treatment approach for patients with BIA-ALCL, providers should consider current clinical practice guidelines, such as those from the National Comprehensive Cancer Network (included in the guidelines for T-cell lymphomas) or the Plastic Surgery Foundation.

Finally, providers should report all confirmed cases of BIA-ALCL to the FDA and to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma (ALCL) Etiology and Epidemiology (PROFILE Registry).

Photo by Rhoda Baer

A new study indicates that adolescent and young adult (AYA) cancer survivors continue to face social difficulties for more than 2 years after their diagnosis.

The research, published in Cancer, suggests these patients may see some improvement in their social lives during the first year after diagnosis.

However, their social functioning tends to remain constant after that, leaving them socially impaired relative to their cancer-free peers.

Previous studies have shown that AYAs with cancer experience greater challenges in social functioning than their cancer-free peers or even compared to older cancer patients.

But few studies have examined this phenomenon by following the same patients over time.

Olga Husson, PhD, of the Radboud University Medical Center in The Netherlands, and her colleagues set out to examine changes in social functioning among AYAs in the early years after a cancer diagnosis.

The researchers asked AYA cancer patients at 5 US medical institutions to complete a survey about social functioning within 4 months of their diagnosis, 12 months later, and 24 months later.

There were 141 patients (ages 14 to 39 at diagnosis) who completed the surveys.

The researchers found that, when compared to population norms, the cancer patients had inferior social functioning at all the time points studied.

Among the cancer patients, the mean social functioning score from the Medical Outcomes Study Short Form 36 Health Survey (version 2) was 52.0 around the time of cancer diagnosis, 73.1 at the 12-month follow-up, and 69.2 at the 24-month follow-up. In comparison, the population norm (for people ages 18 to 44) is 85.1 (P<0.001 for all time points).

The researchers did note that cancer patients experienced significant improvements in social functioning from baseline to the 12-month follow-up, but there was no further improvement after that.

The researchers also examined the different trajectories of social functioning over time. They found that social functioning improved over time for 47% of the cancer patients but worsened for 13%. In addition, 32% of patients had consistently low social functioning, and 9% had consistently high social functioning.

The cancer patients with consistently low social functioning were more likely to be off treatment at the time of follow-up, report more physical symptoms and higher levels of psychological distress (at both baseline and follow-up), and perceive themselves to receive less social support.

“Reducing physical symptoms and psychological distress and enhancing social support by interventions in the period after treatment may potentially help these young survivors to better reintegrate into society,” Dr Husson said.

Photo by Rhoda Baer

A new study indicates that adolescent and young adult (AYA) cancer survivors continue to face social difficulties for more than 2 years after their diagnosis.

The research, published in Cancer, suggests these patients may see some improvement in their social lives during the first year after diagnosis.

However, their social functioning tends to remain constant after that, leaving them socially impaired relative to their cancer-free peers.

Previous studies have shown that AYAs with cancer experience greater challenges in social functioning than their cancer-free peers or even compared to older cancer patients.

But few studies have examined this phenomenon by following the same patients over time.

Olga Husson, PhD, of the Radboud University Medical Center in The Netherlands, and her colleagues set out to examine changes in social functioning among AYAs in the early years after a cancer diagnosis.

The researchers asked AYA cancer patients at 5 US medical institutions to complete a survey about social functioning within 4 months of their diagnosis, 12 months later, and 24 months later.

There were 141 patients (ages 14 to 39 at diagnosis) who completed the surveys.

The researchers found that, when compared to population norms, the cancer patients had inferior social functioning at all the time points studied.

Among the cancer patients, the mean social functioning score from the Medical Outcomes Study Short Form 36 Health Survey (version 2) was 52.0 around the time of cancer diagnosis, 73.1 at the 12-month follow-up, and 69.2 at the 24-month follow-up. In comparison, the population norm (for people ages 18 to 44) is 85.1 (P<0.001 for all time points).

The researchers did note that cancer patients experienced significant improvements in social functioning from baseline to the 12-month follow-up, but there was no further improvement after that.

The researchers also examined the different trajectories of social functioning over time. They found that social functioning improved over time for 47% of the cancer patients but worsened for 13%. In addition, 32% of patients had consistently low social functioning, and 9% had consistently high social functioning.

The cancer patients with consistently low social functioning were more likely to be off treatment at the time of follow-up, report more physical symptoms and higher levels of psychological distress (at both baseline and follow-up), and perceive themselves to receive less social support.

“Reducing physical symptoms and psychological distress and enhancing social support by interventions in the period after treatment may potentially help these young survivors to better reintegrate into society,” Dr Husson said.

Photo by Rhoda Baer

A new study indicates that adolescent and young adult (AYA) cancer survivors continue to face social difficulties for more than 2 years after their diagnosis.

The research, published in Cancer, suggests these patients may see some improvement in their social lives during the first year after diagnosis.

However, their social functioning tends to remain constant after that, leaving them socially impaired relative to their cancer-free peers.

Previous studies have shown that AYAs with cancer experience greater challenges in social functioning than their cancer-free peers or even compared to older cancer patients.

But few studies have examined this phenomenon by following the same patients over time.

Olga Husson, PhD, of the Radboud University Medical Center in The Netherlands, and her colleagues set out to examine changes in social functioning among AYAs in the early years after a cancer diagnosis.

The researchers asked AYA cancer patients at 5 US medical institutions to complete a survey about social functioning within 4 months of their diagnosis, 12 months later, and 24 months later.

There were 141 patients (ages 14 to 39 at diagnosis) who completed the surveys.

The researchers found that, when compared to population norms, the cancer patients had inferior social functioning at all the time points studied.

Among the cancer patients, the mean social functioning score from the Medical Outcomes Study Short Form 36 Health Survey (version 2) was 52.0 around the time of cancer diagnosis, 73.1 at the 12-month follow-up, and 69.2 at the 24-month follow-up. In comparison, the population norm (for people ages 18 to 44) is 85.1 (P<0.001 for all time points).

The researchers did note that cancer patients experienced significant improvements in social functioning from baseline to the 12-month follow-up, but there was no further improvement after that.

The researchers also examined the different trajectories of social functioning over time. They found that social functioning improved over time for 47% of the cancer patients but worsened for 13%. In addition, 32% of patients had consistently low social functioning, and 9% had consistently high social functioning.

The cancer patients with consistently low social functioning were more likely to be off treatment at the time of follow-up, report more physical symptoms and higher levels of psychological distress (at both baseline and follow-up), and perceive themselves to receive less social support.

“Reducing physical symptoms and psychological distress and enhancing social support by interventions in the period after treatment may potentially help these young survivors to better reintegrate into society,” Dr Husson said.

Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma, based on the results of a pilot study of 27 patients.

Of study participants whose multiple myeloma at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001), reported Anna Oberle of University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and her associates. The findings were published in Haematologica.

“Taken together, our pilot study gives valuable biological insights into the circulating cellular and cell-free compartments explorable by ‘liquid biopsy’ in multiple myeloma,” the investigators wrote. Levels of V(D)J-positive circulating myeloma cells and cell-free DNA might decline faster in response to effective therapy than the “relatively inert M-protein,” and might therefore be a better way to immediately estimate treatment efficacy or predict minimum residual disease negativity, they added (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.161414).

Novel multiple myeloma therapies are inducing deeper, longer responses, which highlights the need for minimum residual disease monitoring, the researchers said. Next-generation sequencing of the clonotypic V(D)J immunoglobulin rearrangement has shown promise but requires painful bone marrow sampling. A minimally invasive alternative is to monitor for circulating myeloma cells (cmc) or cell-free myeloma (cfm). To investigate the feasibility of this technique, the researchers used next-generation sequencing to define the myeloma V(D)J rearrangement in bone marrow and to track sequential peripheral blood samples from multiple myeloma patients before and during treatment. Next-generation sequencing was performed with an Illumina MiSeq sequencer with 500 or 600 cycle single-indexed, paired-end runs.

After treatment initiation, 47% of follow-up peripheral blood samples were positive for cmc-V(D)J, cfm-V(D)J, or both, the researchers said. They found a clear link between poor remission status assessed by M-protein based IMWG criteria and positive cmc-V(D)J sampling, with a regression coefficient of 1.60 (95% CI, 0.68 to 2.50; P = .002). Poor remission status was also associated with evidence of cfm-V(D)J (regression coefficient 1.49; 95% CI, 0.70 to 2.27; P = .001).

“About half of partial responders showed complete clearance of circulating myeloma cells-/cell-free myeloma DNA -V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover, and therefore decline more rapidly after initiation of effective treatment,” the researchers emphasized. Also, in 30% of cases, patients were positive for only one of the two V(D)J measures, suggesting that cfm-V(D)J might reflect overall tumor burden, not just circulating tumor cells, they added. “Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma,” they concluded.

Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.

Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma, based on the results of a pilot study of 27 patients.

Of study participants whose multiple myeloma at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001), reported Anna Oberle of University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and her associates. The findings were published in Haematologica.

“Taken together, our pilot study gives valuable biological insights into the circulating cellular and cell-free compartments explorable by ‘liquid biopsy’ in multiple myeloma,” the investigators wrote. Levels of V(D)J-positive circulating myeloma cells and cell-free DNA might decline faster in response to effective therapy than the “relatively inert M-protein,” and might therefore be a better way to immediately estimate treatment efficacy or predict minimum residual disease negativity, they added (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.161414).

Novel multiple myeloma therapies are inducing deeper, longer responses, which highlights the need for minimum residual disease monitoring, the researchers said. Next-generation sequencing of the clonotypic V(D)J immunoglobulin rearrangement has shown promise but requires painful bone marrow sampling. A minimally invasive alternative is to monitor for circulating myeloma cells (cmc) or cell-free myeloma (cfm). To investigate the feasibility of this technique, the researchers used next-generation sequencing to define the myeloma V(D)J rearrangement in bone marrow and to track sequential peripheral blood samples from multiple myeloma patients before and during treatment. Next-generation sequencing was performed with an Illumina MiSeq sequencer with 500 or 600 cycle single-indexed, paired-end runs.

After treatment initiation, 47% of follow-up peripheral blood samples were positive for cmc-V(D)J, cfm-V(D)J, or both, the researchers said. They found a clear link between poor remission status assessed by M-protein based IMWG criteria and positive cmc-V(D)J sampling, with a regression coefficient of 1.60 (95% CI, 0.68 to 2.50; P = .002). Poor remission status was also associated with evidence of cfm-V(D)J (regression coefficient 1.49; 95% CI, 0.70 to 2.27; P = .001).

“About half of partial responders showed complete clearance of circulating myeloma cells-/cell-free myeloma DNA -V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover, and therefore decline more rapidly after initiation of effective treatment,” the researchers emphasized. Also, in 30% of cases, patients were positive for only one of the two V(D)J measures, suggesting that cfm-V(D)J might reflect overall tumor burden, not just circulating tumor cells, they added. “Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma,” they concluded.

Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.

Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma, based on the results of a pilot study of 27 patients.

Of study participants whose multiple myeloma at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001), reported Anna Oberle of University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and her associates. The findings were published in Haematologica.

“Taken together, our pilot study gives valuable biological insights into the circulating cellular and cell-free compartments explorable by ‘liquid biopsy’ in multiple myeloma,” the investigators wrote. Levels of V(D)J-positive circulating myeloma cells and cell-free DNA might decline faster in response to effective therapy than the “relatively inert M-protein,” and might therefore be a better way to immediately estimate treatment efficacy or predict minimum residual disease negativity, they added (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.161414).

Novel multiple myeloma therapies are inducing deeper, longer responses, which highlights the need for minimum residual disease monitoring, the researchers said. Next-generation sequencing of the clonotypic V(D)J immunoglobulin rearrangement has shown promise but requires painful bone marrow sampling. A minimally invasive alternative is to monitor for circulating myeloma cells (cmc) or cell-free myeloma (cfm). To investigate the feasibility of this technique, the researchers used next-generation sequencing to define the myeloma V(D)J rearrangement in bone marrow and to track sequential peripheral blood samples from multiple myeloma patients before and during treatment. Next-generation sequencing was performed with an Illumina MiSeq sequencer with 500 or 600 cycle single-indexed, paired-end runs.

After treatment initiation, 47% of follow-up peripheral blood samples were positive for cmc-V(D)J, cfm-V(D)J, or both, the researchers said. They found a clear link between poor remission status assessed by M-protein based IMWG criteria and positive cmc-V(D)J sampling, with a regression coefficient of 1.60 (95% CI, 0.68 to 2.50; P = .002). Poor remission status was also associated with evidence of cfm-V(D)J (regression coefficient 1.49; 95% CI, 0.70 to 2.27; P = .001).

“About half of partial responders showed complete clearance of circulating myeloma cells-/cell-free myeloma DNA -V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover, and therefore decline more rapidly after initiation of effective treatment,” the researchers emphasized. Also, in 30% of cases, patients were positive for only one of the two V(D)J measures, suggesting that cfm-V(D)J might reflect overall tumor burden, not just circulating tumor cells, they added. “Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma,” they concluded.

Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.

Micrograph showing diffuse large B-cell lymphoma

When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.

In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.

Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.

This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.

Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.

Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.

The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).

Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.

Response

The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).

Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.

Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.

Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.

The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).

The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).

High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).

Toxicity

Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).

The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.

One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.

One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.

The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).

In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).

Micrograph showing diffuse large B-cell lymphoma

When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.

In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.

Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.

This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.

Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.

Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.

The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).

Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.

Response

The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).

Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.

Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.

Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.

The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).

The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).

High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).

Toxicity

Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).

The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.

One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.

One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.

The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).

In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).

Micrograph showing diffuse large B-cell lymphoma

When given after low-dose chemotherapy, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can produce durable complete responses (CRs) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to research published in the Journal of Clinical Oncology.

In this phase 1 study, the overall response rate was 73%, and 50% of patients had an ongoing CR at last follow-up.

Fifty-five percent of patients experienced grade 3/4 neurologic toxicities, though these events eventually resolved.

This research was conducted under a cooperative research and development agreement between the National Cancer Institute and Kite Pharma, Inc.

Kite is developing the CAR T-cell therapy axicabtagene ciloleucel (formerly known as KTE-C19), and the therapy tested in this trial has the same CAR construct as axicabtagene ciloleucel.

Results from this study (NCT00924326) were previously published in the Journal of Clinical Oncology in 2014.

The current report included 22 patients with relapsed/refractory NHL. Seventeen patients had diffuse large B-cell lymphoma (DLBCL), 2 had primary mediastinal B-cell lymphoma (PMBCL), 2 had follicular lymphoma (FL), and 1 had mantle cell lymphoma (MCL).

Patients received a single dose of CAR T cells 2 days after a low-dose chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine.

Response

The overall response rate was 73% (16/22), with a CR rate of 55% (n=12) and a partial response (PR) rate of 18% (n=4).

Among patients with DLBCL, there were 9 CRs, 4 PRs, 1 patient with stable disease, and 3 patients with progressive disease.

Both FL patients achieved a CR, as did the patient with MCL. One patient with PMBCL had stable disease, and the other progressed.

Eleven of the 12 CRs are ongoing, with durations ranging from more than 7 months to more than 24 months. The median duration of CR is 12.5 months.

The researchers found that serum IL-15 levels and CAR T-cell expansion correlated with treatment response (CR or PR).

The median peak blood CAR+ cell level was 98/μL in patients who achieved a response and 15/μL in those who did not (P=0.027).

High serum IL-15 levels were significantly associated with high peak blood CAR+ cell levels (P=0.001) and response (P<0.001).

Toxicity

Fifty-five percent of patients had grade 3 or 4 neurologic toxicities, the most common of which were dysphasia (n=9) and confusion (n=8).

The researchers said all acute toxicities resolved completely, and none of the patients died as a result of toxicity.

One patient experienced vision loss 3 months after receiving CAR T-cell therapy. The researchers said they could not confirm the cause of the vision loss, but it is consistent with fludarabine toxicity.

One patient developed myelodysplastic syndrome, which was thought to be related to prior therapy.

The researchers noted that patients who experienced grade 3/4 neurologic toxicity had significantly higher levels of blood CAR+ cells than patients who had neurologic toxicities of a lower grade (P=0.003).

In addition, peak levels of serum IL-10 and IL-15 were higher in patients with grade 3/4 neurologic toxicities (P=0.006 and 0.014, respectively).

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

Pembrolizumab is now approved for the treatment of adults and children who have refractory classical Hodgkin lymphoma, or who have relapsed after three or more prior lines of therapy, the Food and Drug Administration announced on March 14.

Pembrolizumab (Keytruda) is a humanized monoclonal antibody administered intravenously. According to a press release from Merck, the manufacturer of Keytruda, the approval is based on data from 210 patients aged 18 years and older in the KEYNOTE-087 trial, which found an overall response rate of 69% among patients who received 200 mg of the drug every 3 weeks. Among responders, the median duration of response was 11.1 months.

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Cpl Si Longworth RLC

People who have served in the Armed Forces do not have an increased risk of leukemia or lymphoma, according to research published in Cancer Epidemiology.

Researchers analyzed the long-term risks of developing leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in veterans living in Scotland.

At a mean 30 years of follow-up, there were no significant differences in the risk of the aforementioned malignancies between veterans and non-veterans in Scotland.

This retrospective study included 56,205 veterans and 172,741 non-veterans.

The veterans’ earliest date of entering service was January 1960, and the latest date of leaving service was December 2012.

At a mean follow-up of 29.3 years, 294 (0.52%) veterans and 974 (0.56%) non-veterans were diagnosed with leukemia, HL, or NHL.

There were 125 (0.22%) cases of leukemia in veterans and 365 (0.21%) in non-veterans. There were 59 (0.10%) cases of HL in veterans and 182 (0.11%) in non-veterans. And there were 144 (0.26%) cases of NHL in veterans and 538 (0.31%) in non-veterans.

There was no significant difference in the risk of all 3 cancer types between the veterans and non-veterans. The unadjusted hazard ratio (HR) was 0.96 (P=0.541).

There were no significant differences in an adjusted analysis either. (The analysis was adjusted for regional deprivation, which takes into account information on income, employment, health, education, housing, crime, and access to services.)

The adjusted HR was 1.03 (P=0.773) for leukemias, 1.19 (P=0.272) for HL, and 0.86 (P=0.110) for NHL.

“This is an important study which provides reassurance that military service in the last 50 years does not increase people’s risk of leukemia overall,” said study author Beverly Bergman, PhD, of the University of Glasgow in the UK.

“The Armed Forces comply with all relevant health and safety legislation and regulations, and we can now see that their risk is no different from the general population.”

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo courtesy of Merck

The US Food and Drug Administration (FDA) has granted accelerated approval for pembrolizumab (Keytruda) as a treatment for adult and pediatric patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response.

The drug, which is being developed by Merck, previously received FDA approval as a treatment for melanoma, lung cancer, and head and neck cancer.

Now, pembrolizumab has received accelerated approval to treat adult and pediatric patients with refractory cHL or those with cHL who have relapsed after 3 or more prior lines of therapy.

The accelerated approval was based on tumor response rate and durability of response. Continued approval of pembrolizumab for cHL patients may be contingent upon the verification and description of clinical benefit in confirmatory trials.

In adults with cHL, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

In pediatric patients with cHL, pembrolizumab is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Pembrolizumab trials

The FDA’s approval of pembrolizumab in adults with cHL is based on data from the phase 2 KEYNOTE-087 trial. (The following data were provided by Merck.)

The trial enrolled 210 patients who received pembrolizumab at a dose of 200 mg every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months in patients who did not progress.

Fifty-eight percent of patients were refractory to their last prior therapy, including 35% with primary refractory disease and 14% whose disease was refractory to all prior regimens.

Sixty-one percent of patients had undergone prior autologous hematopoietic stem cell transplant, 83% had prior brentuximab use, and 36% had prior radiation therapy.

At a median follow-up of 9.4 months, the overall response rate was 69%, and the complete response rate was 22%. The median duration of response was 11.1 months (range, 0.0+ to 11.1 months).

Five percent of patients discontinued pembrolizumab due to adverse events (AEs), and 26% had dose interruptions due to AEs. Fifteen percent of patients had an AE requiring systemic corticosteroid therapy.

The most common AEs (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Serious AEs occurred in 16% of patients. The most frequent serious AEs (≥1%) were pneumonia, pneumonitis, pyrexia, dyspnea, graft-vs-host disease, and herpes zoster.

Two patients died from causes other than disease progression. One death was a result of graft-vs-host disease after subsequent allogeneic transplant, and the other was from septic shock.

There is limited experience with pembrolizumab in pediatric patients. The efficacy of the drug for pediatric patients was extrapolated from the results in the adult cHL population.

However, there is safety data on pembrolizumab in pediatric patients enrolled in the phase 1/2 KEYNOTE-051 trial. (These data were also provided by Merck.)

The trial included 40 pediatric patients with advanced melanoma or PD-L1–positive advanced, relapsed, or refractory solid tumors or lymphoma. Patients in this trial received pembrolizumab for a median of 43 days (range, 1-414 days).

The safety profile in these patients was similar to the profile in adults. Toxicities that occurred at a higher rate (≥15% difference) in pediatric patients than in adults under age 65 were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Photo by Rhoda Baer

A new study suggests Hodgkin lymphoma (HL) survivors have a high risk of developing a second malignancy, particularly if they have a family history of that malignancy.

The research showed that HL survivors in Sweden were roughly 2.4 times more likely than individuals in the country’s general population to develop a second cancer.

The risk for HL survivors remained high 30 years after treatment, and the risk was even greater in HL survivors who had a family history of specific cancers.

“The vast majority of patients with Hodgkin lymphoma are cured with a combination of chemotherapy and radiotherapy,” said study author Amit Sud, MBChB, of The Institute of Cancer Research, London in the UK.

“Our research has shown that these patients are at substantially increased risk of a second cancer later in life and particularly if they have a family history of cancer.”

Dr Sud and his colleagues described this research in the Journal of Clinical Oncology.

The team analyzed data from the Swedish Family-Cancer Project Database. They identified 9522 HL patients diagnosed between 1965 and 2013. During a median follow-up of 12.6 years, there were 1215 second cancers in 1121 HL patients (12%).

Compared to the general population, the HL patients had a significantly higher risk of all second malignancies, with a standardized incident ratio (SIR) of 2.39 and an absolute excess risk of 71.2 cases per 10,000 person-years.

Cancer types

HL patients had a significantly increased risk of several malignancies. The overall SIRs were as follows:

• NHL—7.99
• Leukemia—6.46
• Connective tissue cancer—5.73
• Thyroid cancer—5.13
• Squamous cell carcinoma—4.44
• Lung cancer—3.61
• Pharyngeal cancer—3.52
• Esophageal cancer—2.62
• Brain cancer—2.58
• Breast cancer—2.52
• Colon cancer—2.21
• Pancreatic cancer—2.09
• Melanoma—2.08
• Colorectal cancer—1.85
• Stomach cancer—1.78
• Bladder cancer—1.57
• Prostate cancer—1.21.

The researchers calculated SIRs over time and found the risk for many of the cancers remained high over 30 years following HL treatment.

Family history

The researchers identified 28,277 first-degree relatives of the HL survivors. Thirty percent of HL survivors (n=2785) had 1 or more first-degree relatives with a family history of cancer.

The SIR for cancers was 1.02 in the relatives. The SIR for second cancers was 2.83 for HL survivors who had first-degree relatives with cancer and 2.16 for HL survivors who did not have any first-degree relatives with cancer.

The researchers said the increased risk of second malignancy was correlated with the number of first-degree relatives with cancer.

The SIR was 2.67 for HL patients who had a single first-degree relative with cancer and 3.40 for HL patients who had 2 or more first-degree relatives with cancer.

The SIRs for different cancer types (for HL patients with at least 1 first-degree relative with cancer and no first-degree relatives with cancer, respectively) were as follows:

• NHL—14.43 vs 7.83
• Leukemia—14.31 vs 6.37
• Squamous cell carcinoma—10.85 vs 4.30
• Lung cancer—11.24 vs 3.39
• Breast cancer—4.36 vs 2.36
• Colorectal cancer—3.71 vs 1.76.

Sex and age

The researchers found significant differences in the SIRs for second cancers between HL patients diagnosed before the age of 35 and those diagnosed after age 35.

For men, the SIRs were:

• All cancers—4.26 for <35, 2.08 for ≥ 35
• Colorectal cancer—4.07 for < 35, 1.73 for ≥35
• Lung cancer—6.16 for < 35, 3.20 for ≥35
• Breast cancer—12.60 for < 35, 4.58 for ≥35
• Squamous cell carcinoma—5.89 for < 35, 3.96 for ≥35
• NHL—15.9 for < 35, 6.93 for ≥35
• Leukemia—12.15 for < 35, 5.57 for ≥35.

For women, the SIRs were:

• All cancers—4.61 for <35, 1.73 for ≥ 35
• Colorectal cancer—1.31 for < 35, 1.65 for ≥35
• Lung cancer—8.84 for < 35, 2.50 for ≥35
• Breast cancer—6.00 for < 35, 1.14 for ≥35
• Squamous cell carcinoma—6.37 for < 35, 4.87 for ≥35
• NHL—6.23 for < 35, 6.55 for ≥35
• Leukemia—10.36 for < 35, 4.51 for ≥35.

“Younger women who have been treated with radiotherapy to the chest for Hodgkin lymphoma are already screened for breast cancer, but our study suggests that we should be looking at ways of monitoring survivors for other forms of cancer too, and potentially offering preventative interventions,” Dr Sud said.

“After patients are cured, they no longer encounter oncologists, so it’s important that other healthcare providers are aware of the increased risk to Hodgkin lymphoma survivors to improve early diagnosis of second cancers.”

Photo by Rhoda Baer

A new study suggests Hodgkin lymphoma (HL) survivors have a high risk of developing a second malignancy, particularly if they have a family history of that malignancy.

The research showed that HL survivors in Sweden were roughly 2.4 times more likely than individuals in the country’s general population to develop a second cancer.

The risk for HL survivors remained high 30 years after treatment, and the risk was even greater in HL survivors who had a family history of specific cancers.

“The vast majority of patients with Hodgkin lymphoma are cured with a combination of chemotherapy and radiotherapy,” said study author Amit Sud, MBChB, of The Institute of Cancer Research, London in the UK.

“Our research has shown that these patients are at substantially increased risk of a second cancer later in life and particularly if they have a family history of cancer.”

Dr Sud and his colleagues described this research in the Journal of Clinical Oncology.

The team analyzed data from the Swedish Family-Cancer Project Database. They identified 9522 HL patients diagnosed between 1965 and 2013. During a median follow-up of 12.6 years, there were 1215 second cancers in 1121 HL patients (12%).

Compared to the general population, the HL patients had a significantly higher risk of all second malignancies, with a standardized incident ratio (SIR) of 2.39 and an absolute excess risk of 71.2 cases per 10,000 person-years.

Cancer types

HL patients had a significantly increased risk of several malignancies. The overall SIRs were as follows:

• NHL—7.99
• Leukemia—6.46
• Connective tissue cancer—5.73
• Thyroid cancer—5.13
• Squamous cell carcinoma—4.44
• Lung cancer—3.61
• Pharyngeal cancer—3.52
• Esophageal cancer—2.62
• Brain cancer—2.58
• Breast cancer—2.52
• Colon cancer—2.21
• Pancreatic cancer—2.09
• Melanoma—2.08
• Colorectal cancer—1.85
• Stomach cancer—1.78
• Bladder cancer—1.57
• Prostate cancer—1.21.

The researchers calculated SIRs over time and found the risk for many of the cancers remained high over 30 years following HL treatment.

Family history

The researchers identified 28,277 first-degree relatives of the HL survivors. Thirty percent of HL survivors (n=2785) had 1 or more first-degree relatives with a family history of cancer.

The SIR for cancers was 1.02 in the relatives. The SIR for second cancers was 2.83 for HL survivors who had first-degree relatives with cancer and 2.16 for HL survivors who did not have any first-degree relatives with cancer.

The researchers said the increased risk of second malignancy was correlated with the number of first-degree relatives with cancer.

The SIR was 2.67 for HL patients who had a single first-degree relative with cancer and 3.40 for HL patients who had 2 or more first-degree relatives with cancer.

The SIRs for different cancer types (for HL patients with at least 1 first-degree relative with cancer and no first-degree relatives with cancer, respectively) were as follows:

• NHL—14.43 vs 7.83
• Leukemia—14.31 vs 6.37
• Squamous cell carcinoma—10.85 vs 4.30
• Lung cancer—11.24 vs 3.39
• Breast cancer—4.36 vs 2.36
• Colorectal cancer—3.71 vs 1.76.

Sex and age

The researchers found significant differences in the SIRs for second cancers between HL patients diagnosed before the age of 35 and those diagnosed after age 35.

For men, the SIRs were:

• All cancers—4.26 for <35, 2.08 for ≥ 35
• Colorectal cancer—4.07 for < 35, 1.73 for ≥35
• Lung cancer—6.16 for < 35, 3.20 for ≥35
• Breast cancer—12.60 for < 35, 4.58 for ≥35
• Squamous cell carcinoma—5.89 for < 35, 3.96 for ≥35
• NHL—15.9 for < 35, 6.93 for ≥35
• Leukemia—12.15 for < 35, 5.57 for ≥35.

For women, the SIRs were:

• All cancers—4.61 for <35, 1.73 for ≥ 35
• Colorectal cancer—1.31 for < 35, 1.65 for ≥35
• Lung cancer—8.84 for < 35, 2.50 for ≥35
• Breast cancer—6.00 for < 35, 1.14 for ≥35
• Squamous cell carcinoma—6.37 for < 35, 4.87 for ≥35
• NHL—6.23 for < 35, 6.55 for ≥35
• Leukemia—10.36 for < 35, 4.51 for ≥35.

“Younger women who have been treated with radiotherapy to the chest for Hodgkin lymphoma are already screened for breast cancer, but our study suggests that we should be looking at ways of monitoring survivors for other forms of cancer too, and potentially offering preventative interventions,” Dr Sud said.

“After patients are cured, they no longer encounter oncologists, so it’s important that other healthcare providers are aware of the increased risk to Hodgkin lymphoma survivors to improve early diagnosis of second cancers.”

Photo by Rhoda Baer

A new study suggests Hodgkin lymphoma (HL) survivors have a high risk of developing a second malignancy, particularly if they have a family history of that malignancy.

The research showed that HL survivors in Sweden were roughly 2.4 times more likely than individuals in the country’s general population to develop a second cancer.

The risk for HL survivors remained high 30 years after treatment, and the risk was even greater in HL survivors who had a family history of specific cancers.

“The vast majority of patients with Hodgkin lymphoma are cured with a combination of chemotherapy and radiotherapy,” said study author Amit Sud, MBChB, of The Institute of Cancer Research, London in the UK.

“Our research has shown that these patients are at substantially increased risk of a second cancer later in life and particularly if they have a family history of cancer.”

Dr Sud and his colleagues described this research in the Journal of Clinical Oncology.

The team analyzed data from the Swedish Family-Cancer Project Database. They identified 9522 HL patients diagnosed between 1965 and 2013. During a median follow-up of 12.6 years, there were 1215 second cancers in 1121 HL patients (12%).

Compared to the general population, the HL patients had a significantly higher risk of all second malignancies, with a standardized incident ratio (SIR) of 2.39 and an absolute excess risk of 71.2 cases per 10,000 person-years.

Cancer types

HL patients had a significantly increased risk of several malignancies. The overall SIRs were as follows:

• NHL—7.99
• Leukemia—6.46
• Connective tissue cancer—5.73
• Thyroid cancer—5.13
• Squamous cell carcinoma—4.44
• Lung cancer—3.61
• Pharyngeal cancer—3.52
• Esophageal cancer—2.62
• Brain cancer—2.58
• Breast cancer—2.52
• Colon cancer—2.21
• Pancreatic cancer—2.09
• Melanoma—2.08
• Colorectal cancer—1.85
• Stomach cancer—1.78
• Bladder cancer—1.57
• Prostate cancer—1.21.

The researchers calculated SIRs over time and found the risk for many of the cancers remained high over 30 years following HL treatment.

Family history

The researchers identified 28,277 first-degree relatives of the HL survivors. Thirty percent of HL survivors (n=2785) had 1 or more first-degree relatives with a family history of cancer.

The SIR for cancers was 1.02 in the relatives. The SIR for second cancers was 2.83 for HL survivors who had first-degree relatives with cancer and 2.16 for HL survivors who did not have any first-degree relatives with cancer.

The researchers said the increased risk of second malignancy was correlated with the number of first-degree relatives with cancer.

The SIR was 2.67 for HL patients who had a single first-degree relative with cancer and 3.40 for HL patients who had 2 or more first-degree relatives with cancer.

The SIRs for different cancer types (for HL patients with at least 1 first-degree relative with cancer and no first-degree relatives with cancer, respectively) were as follows:

• NHL—14.43 vs 7.83
• Leukemia—14.31 vs 6.37
• Squamous cell carcinoma—10.85 vs 4.30
• Lung cancer—11.24 vs 3.39
• Breast cancer—4.36 vs 2.36
• Colorectal cancer—3.71 vs 1.76.

Sex and age

The researchers found significant differences in the SIRs for second cancers between HL patients diagnosed before the age of 35 and those diagnosed after age 35.

For men, the SIRs were:

• All cancers—4.26 for <35, 2.08 for ≥ 35
• Colorectal cancer—4.07 for < 35, 1.73 for ≥35
• Lung cancer—6.16 for < 35, 3.20 for ≥35
• Breast cancer—12.60 for < 35, 4.58 for ≥35
• Squamous cell carcinoma—5.89 for < 35, 3.96 for ≥35
• NHL—15.9 for < 35, 6.93 for ≥35
• Leukemia—12.15 for < 35, 5.57 for ≥35.

For women, the SIRs were:

• All cancers—4.61 for <35, 1.73 for ≥ 35
• Colorectal cancer—1.31 for < 35, 1.65 for ≥35
• Lung cancer—8.84 for < 35, 2.50 for ≥35
• Breast cancer—6.00 for < 35, 1.14 for ≥35
• Squamous cell carcinoma—6.37 for < 35, 4.87 for ≥35
• NHL—6.23 for < 35, 6.55 for ≥35
• Leukemia—10.36 for < 35, 4.51 for ≥35.

“Younger women who have been treated with radiotherapy to the chest for Hodgkin lymphoma are already screened for breast cancer, but our study suggests that we should be looking at ways of monitoring survivors for other forms of cancer too, and potentially offering preventative interventions,” Dr Sud said.

“After patients are cured, they no longer encounter oncologists, so it’s important that other healthcare providers are aware of the increased risk to Hodgkin lymphoma survivors to improve early diagnosis of second cancers.”

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).

Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.

While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.

However, no new patients may be enrolled in selinexor trials until the hold is lifted.

The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.

Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.

As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold.  By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.

Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.

About selinexor

Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce apoptosis in cancer cells while largely sparing normal cells.

To date, more than 1900 patients have been treated with selinexor. The drug is currently being evaluated in several trials across multiple cancer indications.

One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.

The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.

STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.

Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.

Additional phase 1, 2, and 3 studies are ongoing or currently planned. 

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).

Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.

While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.

However, no new patients may be enrolled in selinexor trials until the hold is lifted.

The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.

Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.

As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold.  By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.

Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.

About selinexor

Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce apoptosis in cancer cells while largely sparing normal cells.

To date, more than 1900 patients have been treated with selinexor. The drug is currently being evaluated in several trials across multiple cancer indications.

One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.

The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.

STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.

Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.

Additional phase 1, 2, and 3 studies are ongoing or currently planned. 

Photo by Esther Dyson

The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).

Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.

While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.

However, no new patients may be enrolled in selinexor trials until the hold is lifted.

The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.

Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.

As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold.  By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.

Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.

About selinexor

Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce apoptosis in cancer cells while largely sparing normal cells.

To date, more than 1900 patients have been treated with selinexor. The drug is currently being evaluated in several trials across multiple cancer indications.

One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.

The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.

STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.

Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.

Additional phase 1, 2, and 3 studies are ongoing or currently planned.