Multiple Myeloma

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Younger age of onset and the use of autologous hematopoietic stem cell transplant (ASCT) treatment were key factors improving the length of survival of newly diagnosed, active multiple myeloma (MM) patients, according to the results of a retrospective analysis.

In addition, multivariable analysis showed that a higher level of blood creatinine, the presence of extramedullary disease, a lower level of partial remission, and the use of nonautologous hematopoietic stem cell transplantation were independent risk factors for shorter survival, according to Virginia Bove, MD, of the Asociación Espanola Primera en Socorros Mutuos, Montevideo, Uruguay and colleagues.
 

Dr. Bove and colleagues retrospectively analyzed clinical characteristics, response to treatment, and survival of 282 patients from multiple institutions who had active newly-diagnosed multiple myeloma. They compared the results between patients age 65 years or younger (53.2%) with those older than 65 years and assessed clinical risk factors, as reported online in Hematology, Transfusion, and Cell Therapy.

The main cause of death in all patients was MM progression and the early mortality rate was not different between the younger and older patients. The main cause of early death in older patients was infection, according to the researchers.

Multiple risk factors

“Although MM patients younger than 66 years of age have an aggressive presentation with an advanced stage, high rate of renal failure and extramedullary disease, this did not translate into an inferior [overall survival] and [progression-free survival],” the researchers reported.

The overall response rate was similar between groups (80.6% vs. 81.4%; P = .866), and the overall survival was significantly longer in young patients (median, 65 months vs. 41 months; P = .001) and higher in those who received autologous hematopoietic stem cell transplantation.

Multivariate analysis was performed on data from the younger patients. The results showed that a creatinine level of less than or equal to 2 mg/dL (P = .048), extramedullary disease (P = .001), a lower VGPR (P = .003) and the use of nonautologous hematopoietic stem cell transplantation (P = .048) were all independent risk factors for shorter survival.

“Older age is an independent adverse prognostic factor. Adequate risk identification, frontline treatment based on novel drugs and ASCT are the best strategies to improve outcomes, both in young and old patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Bove V et al. Hematol Transfus Cell Ther. 2020 Aug 20. doi: 10.1016/j.htct.2020.06.014.

Younger age of onset and the use of autologous hematopoietic stem cell transplant (ASCT) treatment were key factors improving the length of survival of newly diagnosed, active multiple myeloma (MM) patients, according to the results of a retrospective analysis.

In addition, multivariable analysis showed that a higher level of blood creatinine, the presence of extramedullary disease, a lower level of partial remission, and the use of nonautologous hematopoietic stem cell transplantation were independent risk factors for shorter survival, according to Virginia Bove, MD, of the Asociación Espanola Primera en Socorros Mutuos, Montevideo, Uruguay and colleagues.
 

Dr. Bove and colleagues retrospectively analyzed clinical characteristics, response to treatment, and survival of 282 patients from multiple institutions who had active newly-diagnosed multiple myeloma. They compared the results between patients age 65 years or younger (53.2%) with those older than 65 years and assessed clinical risk factors, as reported online in Hematology, Transfusion, and Cell Therapy.

The main cause of death in all patients was MM progression and the early mortality rate was not different between the younger and older patients. The main cause of early death in older patients was infection, according to the researchers.

Multiple risk factors

“Although MM patients younger than 66 years of age have an aggressive presentation with an advanced stage, high rate of renal failure and extramedullary disease, this did not translate into an inferior [overall survival] and [progression-free survival],” the researchers reported.

The overall response rate was similar between groups (80.6% vs. 81.4%; P = .866), and the overall survival was significantly longer in young patients (median, 65 months vs. 41 months; P = .001) and higher in those who received autologous hematopoietic stem cell transplantation.

Multivariate analysis was performed on data from the younger patients. The results showed that a creatinine level of less than or equal to 2 mg/dL (P = .048), extramedullary disease (P = .001), a lower VGPR (P = .003) and the use of nonautologous hematopoietic stem cell transplantation (P = .048) were all independent risk factors for shorter survival.

“Older age is an independent adverse prognostic factor. Adequate risk identification, frontline treatment based on novel drugs and ASCT are the best strategies to improve outcomes, both in young and old patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Bove V et al. Hematol Transfus Cell Ther. 2020 Aug 20. doi: 10.1016/j.htct.2020.06.014.

Younger age of onset and the use of autologous hematopoietic stem cell transplant (ASCT) treatment were key factors improving the length of survival of newly diagnosed, active multiple myeloma (MM) patients, according to the results of a retrospective analysis.

In addition, multivariable analysis showed that a higher level of blood creatinine, the presence of extramedullary disease, a lower level of partial remission, and the use of nonautologous hematopoietic stem cell transplantation were independent risk factors for shorter survival, according to Virginia Bove, MD, of the Asociación Espanola Primera en Socorros Mutuos, Montevideo, Uruguay and colleagues.
 

Dr. Bove and colleagues retrospectively analyzed clinical characteristics, response to treatment, and survival of 282 patients from multiple institutions who had active newly-diagnosed multiple myeloma. They compared the results between patients age 65 years or younger (53.2%) with those older than 65 years and assessed clinical risk factors, as reported online in Hematology, Transfusion, and Cell Therapy.

The main cause of death in all patients was MM progression and the early mortality rate was not different between the younger and older patients. The main cause of early death in older patients was infection, according to the researchers.

Multiple risk factors

“Although MM patients younger than 66 years of age have an aggressive presentation with an advanced stage, high rate of renal failure and extramedullary disease, this did not translate into an inferior [overall survival] and [progression-free survival],” the researchers reported.

The overall response rate was similar between groups (80.6% vs. 81.4%; P = .866), and the overall survival was significantly longer in young patients (median, 65 months vs. 41 months; P = .001) and higher in those who received autologous hematopoietic stem cell transplantation.

Multivariate analysis was performed on data from the younger patients. The results showed that a creatinine level of less than or equal to 2 mg/dL (P = .048), extramedullary disease (P = .001), a lower VGPR (P = .003) and the use of nonautologous hematopoietic stem cell transplantation (P = .048) were all independent risk factors for shorter survival.

“Older age is an independent adverse prognostic factor. Adequate risk identification, frontline treatment based on novel drugs and ASCT are the best strategies to improve outcomes, both in young and old patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Bove V et al. Hematol Transfus Cell Ther. 2020 Aug 20. doi: 10.1016/j.htct.2020.06.014.

Elotuzumab-based maintenance therapy may improve the posttransplant response for multiple myeloma (MM), according to the results of a small retrospective study at a single institution.

In addition, the therapies appear to be safely administered even to older patients because of the low rate of adverse effects, as indicated in a report published online in Blood Cells, Molecules and Diseases.

The researchers retrospectively evaluated the outcomes of seven MM patients who were started on elotuzumab-based maintenance (elotuzumab/lenalidomide/dexamethasone, elotuzumab/bortezomib/dexamethasone, or elotuzumab/bortezomib/methylprednisolone) following transplant, according to Xin Wang, MD, of the UMass Memorial Medical Center, Worcester, and colleagues.

The median age was 68 years (ranging from 56 years to 81 years) at the time of transplant, and median lines of induction therapy was 2; three patients (42.9%) had high-risk cytogenetics and five (71.4%) had stage II or greater disease at diagnosis.
 

Promising elotuzumab results

At a median follow-up of 24 months, five patients (71.4%) had improvement in their quality of response. Among all patients, there was a combined complete response (CR) or very good partial response (VGPR) rate increase from 57.1% to 100% (CR = 3, VGPR = 4). VGPR was defined by the researchers as an absence of abnormal immunofixation and soft tissue plasmacytoma without bone marrow biopsy.

All patients were alive without relapse or progression at the time of the final analysis. In terms of adverse effects, grade 3-4 events were observed in three (42.9%) of the patients. None of the patients discontinued the treatment because of intolerance, according to the researchers.

“Our study demonstrates that elotuzumab-based maintenance may deepen response post transplant in MM and can be safely administered even in older patients. Given its unique action and rare side effects, further studies of elotuzumab in the post-transplant setting are warranted,” the researchers concluded.

The study had no outside funding and the researchers reported that they had no disclosures.

[email protected]

SOURCE: Wang X et al. Blood Cells Mol Dis. 2020 Jul 28. doi: 10.1016/j.bcmd.2020.102482.

Elotuzumab-based maintenance therapy may improve the posttransplant response for multiple myeloma (MM), according to the results of a small retrospective study at a single institution.

In addition, the therapies appear to be safely administered even to older patients because of the low rate of adverse effects, as indicated in a report published online in Blood Cells, Molecules and Diseases.

The researchers retrospectively evaluated the outcomes of seven MM patients who were started on elotuzumab-based maintenance (elotuzumab/lenalidomide/dexamethasone, elotuzumab/bortezomib/dexamethasone, or elotuzumab/bortezomib/methylprednisolone) following transplant, according to Xin Wang, MD, of the UMass Memorial Medical Center, Worcester, and colleagues.

The median age was 68 years (ranging from 56 years to 81 years) at the time of transplant, and median lines of induction therapy was 2; three patients (42.9%) had high-risk cytogenetics and five (71.4%) had stage II or greater disease at diagnosis.
 

Promising elotuzumab results

At a median follow-up of 24 months, five patients (71.4%) had improvement in their quality of response. Among all patients, there was a combined complete response (CR) or very good partial response (VGPR) rate increase from 57.1% to 100% (CR = 3, VGPR = 4). VGPR was defined by the researchers as an absence of abnormal immunofixation and soft tissue plasmacytoma without bone marrow biopsy.

All patients were alive without relapse or progression at the time of the final analysis. In terms of adverse effects, grade 3-4 events were observed in three (42.9%) of the patients. None of the patients discontinued the treatment because of intolerance, according to the researchers.

“Our study demonstrates that elotuzumab-based maintenance may deepen response post transplant in MM and can be safely administered even in older patients. Given its unique action and rare side effects, further studies of elotuzumab in the post-transplant setting are warranted,” the researchers concluded.

The study had no outside funding and the researchers reported that they had no disclosures.

[email protected]

SOURCE: Wang X et al. Blood Cells Mol Dis. 2020 Jul 28. doi: 10.1016/j.bcmd.2020.102482.

Elotuzumab-based maintenance therapy may improve the posttransplant response for multiple myeloma (MM), according to the results of a small retrospective study at a single institution.

In addition, the therapies appear to be safely administered even to older patients because of the low rate of adverse effects, as indicated in a report published online in Blood Cells, Molecules and Diseases.

The researchers retrospectively evaluated the outcomes of seven MM patients who were started on elotuzumab-based maintenance (elotuzumab/lenalidomide/dexamethasone, elotuzumab/bortezomib/dexamethasone, or elotuzumab/bortezomib/methylprednisolone) following transplant, according to Xin Wang, MD, of the UMass Memorial Medical Center, Worcester, and colleagues.

The median age was 68 years (ranging from 56 years to 81 years) at the time of transplant, and median lines of induction therapy was 2; three patients (42.9%) had high-risk cytogenetics and five (71.4%) had stage II or greater disease at diagnosis.
 

Promising elotuzumab results

At a median follow-up of 24 months, five patients (71.4%) had improvement in their quality of response. Among all patients, there was a combined complete response (CR) or very good partial response (VGPR) rate increase from 57.1% to 100% (CR = 3, VGPR = 4). VGPR was defined by the researchers as an absence of abnormal immunofixation and soft tissue plasmacytoma without bone marrow biopsy.

All patients were alive without relapse or progression at the time of the final analysis. In terms of adverse effects, grade 3-4 events were observed in three (42.9%) of the patients. None of the patients discontinued the treatment because of intolerance, according to the researchers.

“Our study demonstrates that elotuzumab-based maintenance may deepen response post transplant in MM and can be safely administered even in older patients. Given its unique action and rare side effects, further studies of elotuzumab in the post-transplant setting are warranted,” the researchers concluded.

The study had no outside funding and the researchers reported that they had no disclosures.

[email protected]

SOURCE: Wang X et al. Blood Cells Mol Dis. 2020 Jul 28. doi: 10.1016/j.bcmd.2020.102482.

The first-in-class drug belantamab mafodotin (Blenrep) has been granted an accelerated approval by the Food and Drug Administration for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

This follows a recommendation for approval on July 15 by an FDA advisory committee, which voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

The product has a novel mechanism of action: it targets B-cell maturation antigen (BCMA), a protein that is present on the surface of virtually all multiple myeloma cells but is absent from normal B cells.

The drug had already received an FDA breakthrough therapy designation, which facilitates the development of drugs that have shown clinical promise for conditions in which there is significant unmet need.

Belantamab mafodotin was recommended for conditional marketing approval in the European Union on July 24 and was accepted into the European Medicines Agency PRIME scheme for medicines that have potential to address unmet medical needs.

The new drug is indicated for patients with refractory or relapsed multiple myeloma who have already tried treatment with one of the three major classes of drugs, namely, an immunomolatory agent, a proteasome inhibitor, and a CD38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA comments. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

“While treatable, refractory multiple myeloma is a significant clinical challenge with poor outcomes for patients whose disease has become resistant to the current standard of care,” commented Sagar Lonial, MD, chief medical officer of the Winship Cancer Institute of Emory University, Atlanta, chair of the department of hematology and medical oncology at Emory, and a principal investigator for the clinical trial that led to the approval.

“Due to the limited options currently available, these patients are often retreated with drugs from the same classes after they relapse, which is why the approval of belantamab mafodotin, the first anti-BCMA therapy, is significant for both patients and physicians alike,” he said.

The product is an antibody-drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethyl auristatin F. It homes in on BCMA on myeloma cell surfaces. Once inside the myeloma cell, the cytotoxic agent is released, leading to apoptosis, the programmed death of the cancerous plasma cells.
 

Approval based on response rates

The accelerated approval from the FDA and the recommendation for conditional approval from the EMA are based on results for overall response rate and duration of response from a phase 2, open-label, randomized, two-arm study known as DREAMM-2. Both agencies said that they are waiting for further data on clinical benefit from ongoing trials.

The DREAMM-2 study investigated the efficacy and safety of two doses of belantamab mafodotin in multiple myeloma patients whose disease was still active after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results from this study were published in The Lancet Oncology in December. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The median duration of response had not been reached at the 6-month analysis, but for 73% of responders, DoR was ≥6 months.

The most commonly reported adverse events (≥20%) were keratopathy (changes in the cornea), decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue, the manufacturer notes.
 

Ocular toxicity

One of the most common adverse events with this product affects the eyes.

Ocular adverse reactions occurred in 77% of the 218 patients in the pooled safety population and included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%).

Corneal adverse events were monitored with eye exams prior to each dose, allowing dose reductions or interruptions as appropriate, the manufacturer noted. Patients also used preservative-free eyedrops. Keratopathy leading to treatment discontinuation affected 2.1% of patients in the 2.5-mg/kg cohort.

Because of this ocular toxicity, the company has set up a risk evaluation and mitigation strategy (REMS) for the product. This requires education for all physicians who prescribe the product as well as their patients regarding the ocular risks associated with treatment. It also requires monitoring that includes regular ophthalmic examinations. Information about the scheme can be found at www.blenreprems.com.

At the FDA advisory committee meeting last month, one of the panelists, Gita Thanarajasingam, MD, an assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated but for ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some people than current treatments.

“It’s reasonable to leave open the option for decision making. Patients can express their values and preferences,” Dr. Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk-benefit discussion in a REMS program.”

Another panelist, Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it to them” with belantamab.

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep) has been granted an accelerated approval by the Food and Drug Administration for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

This follows a recommendation for approval on July 15 by an FDA advisory committee, which voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

The product has a novel mechanism of action: it targets B-cell maturation antigen (BCMA), a protein that is present on the surface of virtually all multiple myeloma cells but is absent from normal B cells.

The drug had already received an FDA breakthrough therapy designation, which facilitates the development of drugs that have shown clinical promise for conditions in which there is significant unmet need.

Belantamab mafodotin was recommended for conditional marketing approval in the European Union on July 24 and was accepted into the European Medicines Agency PRIME scheme for medicines that have potential to address unmet medical needs.

The new drug is indicated for patients with refractory or relapsed multiple myeloma who have already tried treatment with one of the three major classes of drugs, namely, an immunomolatory agent, a proteasome inhibitor, and a CD38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA comments. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

“While treatable, refractory multiple myeloma is a significant clinical challenge with poor outcomes for patients whose disease has become resistant to the current standard of care,” commented Sagar Lonial, MD, chief medical officer of the Winship Cancer Institute of Emory University, Atlanta, chair of the department of hematology and medical oncology at Emory, and a principal investigator for the clinical trial that led to the approval.

“Due to the limited options currently available, these patients are often retreated with drugs from the same classes after they relapse, which is why the approval of belantamab mafodotin, the first anti-BCMA therapy, is significant for both patients and physicians alike,” he said.

The product is an antibody-drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethyl auristatin F. It homes in on BCMA on myeloma cell surfaces. Once inside the myeloma cell, the cytotoxic agent is released, leading to apoptosis, the programmed death of the cancerous plasma cells.
 

Approval based on response rates

The accelerated approval from the FDA and the recommendation for conditional approval from the EMA are based on results for overall response rate and duration of response from a phase 2, open-label, randomized, two-arm study known as DREAMM-2. Both agencies said that they are waiting for further data on clinical benefit from ongoing trials.

The DREAMM-2 study investigated the efficacy and safety of two doses of belantamab mafodotin in multiple myeloma patients whose disease was still active after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results from this study were published in The Lancet Oncology in December. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The median duration of response had not been reached at the 6-month analysis, but for 73% of responders, DoR was ≥6 months.

The most commonly reported adverse events (≥20%) were keratopathy (changes in the cornea), decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue, the manufacturer notes.
 

Ocular toxicity

One of the most common adverse events with this product affects the eyes.

Ocular adverse reactions occurred in 77% of the 218 patients in the pooled safety population and included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%).

Corneal adverse events were monitored with eye exams prior to each dose, allowing dose reductions or interruptions as appropriate, the manufacturer noted. Patients also used preservative-free eyedrops. Keratopathy leading to treatment discontinuation affected 2.1% of patients in the 2.5-mg/kg cohort.

Because of this ocular toxicity, the company has set up a risk evaluation and mitigation strategy (REMS) for the product. This requires education for all physicians who prescribe the product as well as their patients regarding the ocular risks associated with treatment. It also requires monitoring that includes regular ophthalmic examinations. Information about the scheme can be found at www.blenreprems.com.

At the FDA advisory committee meeting last month, one of the panelists, Gita Thanarajasingam, MD, an assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated but for ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some people than current treatments.

“It’s reasonable to leave open the option for decision making. Patients can express their values and preferences,” Dr. Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk-benefit discussion in a REMS program.”

Another panelist, Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it to them” with belantamab.

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep) has been granted an accelerated approval by the Food and Drug Administration for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

This follows a recommendation for approval on July 15 by an FDA advisory committee, which voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

The product has a novel mechanism of action: it targets B-cell maturation antigen (BCMA), a protein that is present on the surface of virtually all multiple myeloma cells but is absent from normal B cells.

The drug had already received an FDA breakthrough therapy designation, which facilitates the development of drugs that have shown clinical promise for conditions in which there is significant unmet need.

Belantamab mafodotin was recommended for conditional marketing approval in the European Union on July 24 and was accepted into the European Medicines Agency PRIME scheme for medicines that have potential to address unmet medical needs.

The new drug is indicated for patients with refractory or relapsed multiple myeloma who have already tried treatment with one of the three major classes of drugs, namely, an immunomolatory agent, a proteasome inhibitor, and a CD38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA comments. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

“While treatable, refractory multiple myeloma is a significant clinical challenge with poor outcomes for patients whose disease has become resistant to the current standard of care,” commented Sagar Lonial, MD, chief medical officer of the Winship Cancer Institute of Emory University, Atlanta, chair of the department of hematology and medical oncology at Emory, and a principal investigator for the clinical trial that led to the approval.

“Due to the limited options currently available, these patients are often retreated with drugs from the same classes after they relapse, which is why the approval of belantamab mafodotin, the first anti-BCMA therapy, is significant for both patients and physicians alike,” he said.

The product is an antibody-drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethyl auristatin F. It homes in on BCMA on myeloma cell surfaces. Once inside the myeloma cell, the cytotoxic agent is released, leading to apoptosis, the programmed death of the cancerous plasma cells.
 

Approval based on response rates

The accelerated approval from the FDA and the recommendation for conditional approval from the EMA are based on results for overall response rate and duration of response from a phase 2, open-label, randomized, two-arm study known as DREAMM-2. Both agencies said that they are waiting for further data on clinical benefit from ongoing trials.

The DREAMM-2 study investigated the efficacy and safety of two doses of belantamab mafodotin in multiple myeloma patients whose disease was still active after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results from this study were published in The Lancet Oncology in December. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The median duration of response had not been reached at the 6-month analysis, but for 73% of responders, DoR was ≥6 months.

The most commonly reported adverse events (≥20%) were keratopathy (changes in the cornea), decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue, the manufacturer notes.
 

Ocular toxicity

One of the most common adverse events with this product affects the eyes.

Ocular adverse reactions occurred in 77% of the 218 patients in the pooled safety population and included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%).

Corneal adverse events were monitored with eye exams prior to each dose, allowing dose reductions or interruptions as appropriate, the manufacturer noted. Patients also used preservative-free eyedrops. Keratopathy leading to treatment discontinuation affected 2.1% of patients in the 2.5-mg/kg cohort.

Because of this ocular toxicity, the company has set up a risk evaluation and mitigation strategy (REMS) for the product. This requires education for all physicians who prescribe the product as well as their patients regarding the ocular risks associated with treatment. It also requires monitoring that includes regular ophthalmic examinations. Information about the scheme can be found at www.blenreprems.com.

At the FDA advisory committee meeting last month, one of the panelists, Gita Thanarajasingam, MD, an assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated but for ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some people than current treatments.

“It’s reasonable to leave open the option for decision making. Patients can express their values and preferences,” Dr. Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk-benefit discussion in a REMS program.”

Another panelist, Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it to them” with belantamab.

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.

Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.

The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.

Results from open-label study

The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.

The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).

Ocular toxicity

One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.

The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.

At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.

For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.

One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.

“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”

Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
 

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.

Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.

The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.

Results from open-label study

The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.

The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).

Ocular toxicity

One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.

The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.

At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.

For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.

One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.

“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”

Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
 

This article first appeared on Medscape.com.

The first-in-class drug belantamab mafodotin (Blenrep, GlaxoSmithKline) has been recommended for conditional marketing approval in the European Union (EU) for use in the treatment of relapsed and refractory multiple myeloma in patients who have already tried other therapies.

The product was accepted into the European Medicines Agency (EMA) PRIME program for medicines that have potential to address unmet medical needs, the agency noted.

Belantamab mafodotin was also recently recommended for U.S. approval when a Food and Drug Administration advisory committee voted 12-0 in favor of the drug’s benefits outweighing risks in this patient population.

Specifically, these patients with refractory or relapsed multiple myeloma should have already tried treatment with one of the three major classes of drugs, namely an immunomodulatory agent, a proteasome inhibitor, and a CD-38 monoclonal antibody.

For patients who no longer respond to these drugs, the outlook is bleak, the EMA said. There is an unmet medical need for new treatments that improve survival of these patients beyond the currently observed 3 months or less.

Belantamab mafodotin has a novel mechanism of action: It targets B-cell maturation antigen (BCMA), a protein present on the surface of virtually all multiple myeloma cells, but is absent from normal B-cells, thus “making it an ideal drug target,” the agency remarked.

The product is an antibody–drug conjugate that combines a monoclonal antibody that targets BCMA with the cytotoxic agent maleimidocaproyl monomethylauristatin F (mcMMAF). It homes in on BCMA on myeloma cell surfaces, and once inside the myeloma cell, the cytotoxic agent is released leading to apoptosis, the “programmed” death of the cancerous plasma cells, the agency explained.

Results from open-label study

The recommendation for conditional marketing authorization comes from the EMA Committee for Medicinal Products for Human Use (CHMP) and was based on a phase 2, open-label, randomized, two-arm study, DREAMM-2.

The study investigated the efficacy and safety of two doses of belantamab mafodotin in patients with multiple myeloma who still had active disease after three or more lines of therapy and who no longer responded to treatment with immunomodulatory drugs, proteasome inhibitors, and an anti-CD38 monoclonal antibody.

Six-month results were published in December in The Lancet Oncology. The overall response rate was 31% in the cohort given a 2.5-mg/kg dose of the drug; 30 of 97 patients had outcomes that met the study’s positive threshold.

Another 99 patients in DREAMM-2 received a dose of 3.4 mg/kg, which was judged to have a less favorable safety profile.

The EMA has requested further clinical data, including final results from the phase 2 study, as well as results from a confirmatory phase 3 trial comparing belantamab mafodotin with pomalidomide plus low-dose dexamethasone (a standard treatment option for relapsed and refractory multiple myeloma).

Ocular toxicity

One of the most common side effects of the new drug experienced by participants in clinical trials was keratopathy, which affects the cornea. This ocular toxicity was seen at both drug doses.

The EMA noted that patients taking the drug would need to undergo specific ophthalmic examinations so that any findings can be promptly and adequately managed. As for all medicines, a risk management plan (RMP) will ensure rigorous safety monitoring of the medicine once authorized across the European Union, it added.

At the FDA advisory committee meeting, it was noted that 44% of patients in the group that received the 2.5-mg/kg dose experienced at least one episode of severe keratopathy. In some patients, the ocular side effects caused severe vision loss that interfered with patients’ activities of daily living, such as driving and reading, FDA staff said.

For the United States, the manufacturer proposed a risk evaluation and mitigation strategy (REMS) for the detection and treatment of potential complications of belantamab. This includes recommendations for ophthalmic examinations, including assessment of best corrected visual acuity prior to each treatment cycle and promptly for patients with worsening symptoms.

One of the FDA advisory committee panelists, Gita Thanarajasingam, MD, assistant professor of medicine at the Mayo Clinic, in Rochester, Minn., said belantamab appeared to be well tolerated with the exception of ocular toxicity. Physicians need to acknowledge how severe this risk may be for patients while keeping in mind that belantamab still may be more tolerable for some than current treatments, she said.

“It’s reasonable to leave open the option for decision-making. Patients can express their values and preferences,” Thanarajasingam said. “There’s adequate, albeit not complete, information to guide this risk–benefit discussion in a REMS program.”

Heidi D. Klepin, MD, a professor at Wake Forest University Health Sciences, Winston Salem, N.C., agreed that the informed consent process should allow patients “to choose whether the trade-off is worth it” with belantamab.
 

This article first appeared on Medscape.com.

Cardiac dysfunction is a major determinant of poor survival in multiple myeloma (MM) patients with concurrently developed light chain amyloidosis (AL), according to the results of a small cohort study conducted at a single institution.

A total of 53 patients in whom MM and AL were initially diagnosed from July 2006 to June 2016, The cohort comprised 36 men and 17 women with a median age of 59 years; main organ involvement was kidney (72%) and heart (62%). A bortezomib-based regimen was used in 22 patients whose response rate was better than the other 21 patients who received nonbortezomib-based regimens (64% vs. 29%). The median overall survival for the total cohort was 12 months (P < .05), according to the report published in Clinical Lymphoma, Myeloma & Leukemia.

Of particular note, the researchers found that cardiac involvement significantly and adversely affected overall survival (6 vs. 40 months), as did low systolic blood pressure (<90 mm Hg, 3 vs. 8.5 months), according to Yuanyuan Yu and colleagues at the Multiple Myeloma Medical Center of Beijing, Beijing Chao-yang Hospital.

“Although MM-concurrent AL is rare, AL has a negative impact on survival. This study determined that cardiovascular dysfunction caused by AL is the main determinant of shortening survival in patients with MM complicated with AL, and the necessary interventions should be taken to prevent cardiovascular risk,” the researchers concluded.

The work was supported by the Beijing Municipal Health Commission. The authors reported that they had no disclosures.

[email protected]

SOURCE: Yu Y et al. Clin Lymphoma Myeloma Leuk. 2020;20(8):519-25.

Cardiac dysfunction is a major determinant of poor survival in multiple myeloma (MM) patients with concurrently developed light chain amyloidosis (AL), according to the results of a small cohort study conducted at a single institution.

A total of 53 patients in whom MM and AL were initially diagnosed from July 2006 to June 2016, The cohort comprised 36 men and 17 women with a median age of 59 years; main organ involvement was kidney (72%) and heart (62%). A bortezomib-based regimen was used in 22 patients whose response rate was better than the other 21 patients who received nonbortezomib-based regimens (64% vs. 29%). The median overall survival for the total cohort was 12 months (P < .05), according to the report published in Clinical Lymphoma, Myeloma & Leukemia.

Of particular note, the researchers found that cardiac involvement significantly and adversely affected overall survival (6 vs. 40 months), as did low systolic blood pressure (<90 mm Hg, 3 vs. 8.5 months), according to Yuanyuan Yu and colleagues at the Multiple Myeloma Medical Center of Beijing, Beijing Chao-yang Hospital.

“Although MM-concurrent AL is rare, AL has a negative impact on survival. This study determined that cardiovascular dysfunction caused by AL is the main determinant of shortening survival in patients with MM complicated with AL, and the necessary interventions should be taken to prevent cardiovascular risk,” the researchers concluded.

The work was supported by the Beijing Municipal Health Commission. The authors reported that they had no disclosures.

[email protected]

SOURCE: Yu Y et al. Clin Lymphoma Myeloma Leuk. 2020;20(8):519-25.

Cardiac dysfunction is a major determinant of poor survival in multiple myeloma (MM) patients with concurrently developed light chain amyloidosis (AL), according to the results of a small cohort study conducted at a single institution.

A total of 53 patients in whom MM and AL were initially diagnosed from July 2006 to June 2016, The cohort comprised 36 men and 17 women with a median age of 59 years; main organ involvement was kidney (72%) and heart (62%). A bortezomib-based regimen was used in 22 patients whose response rate was better than the other 21 patients who received nonbortezomib-based regimens (64% vs. 29%). The median overall survival for the total cohort was 12 months (P < .05), according to the report published in Clinical Lymphoma, Myeloma & Leukemia.

Of particular note, the researchers found that cardiac involvement significantly and adversely affected overall survival (6 vs. 40 months), as did low systolic blood pressure (<90 mm Hg, 3 vs. 8.5 months), according to Yuanyuan Yu and colleagues at the Multiple Myeloma Medical Center of Beijing, Beijing Chao-yang Hospital.

“Although MM-concurrent AL is rare, AL has a negative impact on survival. This study determined that cardiovascular dysfunction caused by AL is the main determinant of shortening survival in patients with MM complicated with AL, and the necessary interventions should be taken to prevent cardiovascular risk,” the researchers concluded.

The work was supported by the Beijing Municipal Health Commission. The authors reported that they had no disclosures.

[email protected]

SOURCE: Yu Y et al. Clin Lymphoma Myeloma Leuk. 2020;20(8):519-25.

Transitioning from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone therapy increased proteasome inhibitor (PI)–based treatment adherence and duration, according to early results from a clinical trial designed to include patients representing the real-world U.S. multiple myeloma population.

The US MM-6 study was designed to evaluate a novel in-class therapy (iCT) transitioning approach from intravenous to oral treatment in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining health-related quality of life (HRQoL), and improving outcomes in a representative, real-world, community population of multiple myeloma patients, according to Sudhir Manda, MD, of Arizona Oncology/U.S. Oncology Research, Tucson, and colleagues.

Dr. Manda and colleagues reported on the early results of the US MM-6 trial (NCT03173092), which is a community-based, real-world, open-label, single-arm, phase 4 study of adult multiple myeloma patients who do not meet transplant-eligibility criteria, or for whom transplant would be delayed for 2 years or more, and who are receiving first-line bortezomib-based induction. All patients in the study had no evidence of progressive disease after three treatment cycles.

By the data cutoff for the reported analysis, 84 patients had been treated. The patients had a median age of 73 years; 49% were men; 15% black/African American; 10% Hispanic/Latino. A total of 62% of the patients remain on therapy, with a mean duration of total PI therapy of 10.1 months and of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) of 7.3 months.

The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after induction to all-oral ixazomib-Rd.

“The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant [newly diagnosed multiple myeloma] patients,” according to Dr. Manda and colleagues. In addition, “preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients’ HRQoL or treatment satisfaction.”

The study was sponsored by Millennium Pharmaceuticals. Four of the authors are employees of Millennium Pharmaceuticals and several authors disclosed relationships with various pharmaceutical companies, including Millennium Pharmaceuticals.

[email protected]

SOURCE: Manda S et al. Clin Lymphoma Myeloma Leuk. 2020 Jun 30. doi: 10.1016/j.clml.2020.06.024.

Transitioning from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone therapy increased proteasome inhibitor (PI)–based treatment adherence and duration, according to early results from a clinical trial designed to include patients representing the real-world U.S. multiple myeloma population.

The US MM-6 study was designed to evaluate a novel in-class therapy (iCT) transitioning approach from intravenous to oral treatment in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining health-related quality of life (HRQoL), and improving outcomes in a representative, real-world, community population of multiple myeloma patients, according to Sudhir Manda, MD, of Arizona Oncology/U.S. Oncology Research, Tucson, and colleagues.

Dr. Manda and colleagues reported on the early results of the US MM-6 trial (NCT03173092), which is a community-based, real-world, open-label, single-arm, phase 4 study of adult multiple myeloma patients who do not meet transplant-eligibility criteria, or for whom transplant would be delayed for 2 years or more, and who are receiving first-line bortezomib-based induction. All patients in the study had no evidence of progressive disease after three treatment cycles.

By the data cutoff for the reported analysis, 84 patients had been treated. The patients had a median age of 73 years; 49% were men; 15% black/African American; 10% Hispanic/Latino. A total of 62% of the patients remain on therapy, with a mean duration of total PI therapy of 10.1 months and of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) of 7.3 months.

The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after induction to all-oral ixazomib-Rd.

“The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant [newly diagnosed multiple myeloma] patients,” according to Dr. Manda and colleagues. In addition, “preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients’ HRQoL or treatment satisfaction.”

The study was sponsored by Millennium Pharmaceuticals. Four of the authors are employees of Millennium Pharmaceuticals and several authors disclosed relationships with various pharmaceutical companies, including Millennium Pharmaceuticals.

[email protected]

SOURCE: Manda S et al. Clin Lymphoma Myeloma Leuk. 2020 Jun 30. doi: 10.1016/j.clml.2020.06.024.

Transitioning from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone therapy increased proteasome inhibitor (PI)–based treatment adherence and duration, according to early results from a clinical trial designed to include patients representing the real-world U.S. multiple myeloma population.

The US MM-6 study was designed to evaluate a novel in-class therapy (iCT) transitioning approach from intravenous to oral treatment in the community-based setting with the aims of increasing PI-based treatment duration and adherence, maintaining health-related quality of life (HRQoL), and improving outcomes in a representative, real-world, community population of multiple myeloma patients, according to Sudhir Manda, MD, of Arizona Oncology/U.S. Oncology Research, Tucson, and colleagues.

Dr. Manda and colleagues reported on the early results of the US MM-6 trial (NCT03173092), which is a community-based, real-world, open-label, single-arm, phase 4 study of adult multiple myeloma patients who do not meet transplant-eligibility criteria, or for whom transplant would be delayed for 2 years or more, and who are receiving first-line bortezomib-based induction. All patients in the study had no evidence of progressive disease after three treatment cycles.

By the data cutoff for the reported analysis, 84 patients had been treated. The patients had a median age of 73 years; 49% were men; 15% black/African American; 10% Hispanic/Latino. A total of 62% of the patients remain on therapy, with a mean duration of total PI therapy of 10.1 months and of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) of 7.3 months.

The overall response rate was 62% (complete response, 4%; very good partial response, 25%; partial response, 33%) after bortezomib-based induction and 70% (complete response, 26%; very good partial response, 29%; partial response, 15%) after induction to all-oral ixazomib-Rd.

“The use of this novel iCT approach from parenteral bortezomib-based to oral ixazomib-based therapy facilitates long-term PI-based treatment that is well tolerated in real-world, nontransplant [newly diagnosed multiple myeloma] patients,” according to Dr. Manda and colleagues. In addition, “preliminary findings indicate that the iCT approach results in promising efficacy and high medication adherence, with no adverse impact on patients’ HRQoL or treatment satisfaction.”

The study was sponsored by Millennium Pharmaceuticals. Four of the authors are employees of Millennium Pharmaceuticals and several authors disclosed relationships with various pharmaceutical companies, including Millennium Pharmaceuticals.

[email protected]

SOURCE: Manda S et al. Clin Lymphoma Myeloma Leuk. 2020 Jun 30. doi: 10.1016/j.clml.2020.06.024.

The risk of progression or death for patients with relapsed or refractory multiple myeloma was nearly halved with the addition of isatuximab to carfilzomib and dexamethasone, according to an interim analysis of the phase 3 IKEMA trial (NCT03275285).

After a median follow-up of 20.7 months, the median progression-free survival had not been reached for 179 patients treated with isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (together, known as Isa-Kd), compared with 19.5 months for 123 patients treated with carfilzomib and dexamethasone alone (Kd). The hazard ratio for progression free survival with the triple combination was 0.531 (P = .0007), reported coprincipal investigator Phillipe Moreau, MD, from the University Hospital Hôtel-Dieu in Nantes, France.

“The benefit of the triplet combination was observed across subgroups, including patients difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” he said in a late-breaking abstract presentation during the virtual annual congress of the European Hematology Association.

Isatuximab is an immunoglobulin G1 monoclonal antibody targeting a CD38 transmembrane glycoprotein on multiple myeloma cells, with a mechanism of action similar to that of another anti-CD38 antibody, daratumumab (Darzalex). Isatuximab is approved in the United States and Europe in combination with pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma after at least two prior lines of therapy.
 

A ‘me too’ agent?

It’s unclear, however, whether isatuximab offers any additional benefit over daratumumab, an agent approved for use both in front line therapy combinations and for patients with relapsed/refractory disease, said Brea C. Lipe, MD, a multiple myeloma specialist at the University of Rochester (N.Y.) Wilmot Cancer Institute, who was not involved in the study.

“Every time we get a new drug it’s nice to have another option, but it doesn’t really add anything different from daratumumab at this point,” she said in an interview.

Dr. Lipe noted the IKEMA results are similar to those seen in the phase 3 CANDOR trial, comparing carfilzomib, dexamethasone, and daratumumab to carfilzomib/dexamethasone alone in patients with relapsed/refractory myeloma. In addition, it’s unknown whether patients with disease that is refractory to daratumumab could benefit from isatuximab, she said.

Although isatuximab has been touted as offering more rapid and more convenient dosing than daratumumab, the introduction of rapid infusion and subcutaneous administration of daratumumab has negated any theoretical advantage of the newcomer, Dr. Lipe added.
 

Study details

In the IKEMA trial, 302 patients with relapsed/refractory multiple myeloma who’d received one to three prior lines of therapy were stratified by the number of prior lines and by revised Multiple Myeloma International Staging System (R-ISS) and were then randomized on a 3:2 basis to treatment with carfilzomib 20 mg/m² on days 1, 2, 8, 9, 15, and 16 of cycle 1 and 56 mg/m² on the corresponding days of each subsequent cycle plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle, with or without isatuximab. The antibody was dosed 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 then every 2 weeks thereafter.

Treatments were continued until disease progression, unacceptable toxicity, or patient choice intervened.

At a prespecified interim analysis, the trial met its primary endpoint of a minimum 41% risk reduction in the hazard rate for progression free survival (PFS), with an actual risk reduction of 47%.

An analysis of PFS by subgroup showed significant benefits with the triple combination for patients aged 65 years and older, those with baseline estimated glomerular filtration rates below 60 mL/min per 1.73 m², those with more than one prior line of therapy, those who had not previously received a proteasome inhibitor (e.g., bortezomib) or immunomodulatory agent (e.g., lenalidomide), those with high-risk cytogenetic status, and those with R-ISS stage II at study entry.

Overall response rates were similar between the study arms, at 86.6% with Isa-Kd and 82.9% with Kd, but the rate of very good partial responses or better was significantly higher with the triplet, at 72.6% versus 56.1% (P = .0011). The rate of minimal residual disease negativity was also significantly lower with Isa-Kd in the intent-to-treat population, at 29.6% versus 13%, respectively (P = .0004).

Overall survival data were not mature at the time of data cutoff and will be reported later, Dr. Moreau said.

Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 76.8% of patients on the triplet and 67.2% of those on Kd. The incidences of death, serious TEAEs, or adverse events leading to discontinuation of therapy did not differ markedly between the treatment arms, however. Grade 3 or greater cardiac failure occurred in seven patients treated with the triplet (4%) and five treated with Kd (4.1%); respective rates of grade 3 or greater hematologic abnormalities included anemia in 22% and 19.7%, neutropenia in 19.2% and 7.4%, and thrombocytopenia in 29.9% and 23.8%.

The primary completion date for the trial is estimated to occur in November 2020, with final results in November 2023.

The study was sponsored by Sanofi. Dr. Moreau disclosed honoraria and a consulting or advisory role with several companies, not including Sanofi. Dr. Lipe disclosed impending advisory board activity for Janssen.

SOURCE: Moreau P et al. EHA Congress, Abstract LB2603.

The risk of progression or death for patients with relapsed or refractory multiple myeloma was nearly halved with the addition of isatuximab to carfilzomib and dexamethasone, according to an interim analysis of the phase 3 IKEMA trial (NCT03275285).

After a median follow-up of 20.7 months, the median progression-free survival had not been reached for 179 patients treated with isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (together, known as Isa-Kd), compared with 19.5 months for 123 patients treated with carfilzomib and dexamethasone alone (Kd). The hazard ratio for progression free survival with the triple combination was 0.531 (P = .0007), reported coprincipal investigator Phillipe Moreau, MD, from the University Hospital Hôtel-Dieu in Nantes, France.

“The benefit of the triplet combination was observed across subgroups, including patients difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” he said in a late-breaking abstract presentation during the virtual annual congress of the European Hematology Association.

Isatuximab is an immunoglobulin G1 monoclonal antibody targeting a CD38 transmembrane glycoprotein on multiple myeloma cells, with a mechanism of action similar to that of another anti-CD38 antibody, daratumumab (Darzalex). Isatuximab is approved in the United States and Europe in combination with pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma after at least two prior lines of therapy.
 

A ‘me too’ agent?

It’s unclear, however, whether isatuximab offers any additional benefit over daratumumab, an agent approved for use both in front line therapy combinations and for patients with relapsed/refractory disease, said Brea C. Lipe, MD, a multiple myeloma specialist at the University of Rochester (N.Y.) Wilmot Cancer Institute, who was not involved in the study.

“Every time we get a new drug it’s nice to have another option, but it doesn’t really add anything different from daratumumab at this point,” she said in an interview.

Dr. Lipe noted the IKEMA results are similar to those seen in the phase 3 CANDOR trial, comparing carfilzomib, dexamethasone, and daratumumab to carfilzomib/dexamethasone alone in patients with relapsed/refractory myeloma. In addition, it’s unknown whether patients with disease that is refractory to daratumumab could benefit from isatuximab, she said.

Although isatuximab has been touted as offering more rapid and more convenient dosing than daratumumab, the introduction of rapid infusion and subcutaneous administration of daratumumab has negated any theoretical advantage of the newcomer, Dr. Lipe added.
 

Study details

In the IKEMA trial, 302 patients with relapsed/refractory multiple myeloma who’d received one to three prior lines of therapy were stratified by the number of prior lines and by revised Multiple Myeloma International Staging System (R-ISS) and were then randomized on a 3:2 basis to treatment with carfilzomib 20 mg/m² on days 1, 2, 8, 9, 15, and 16 of cycle 1 and 56 mg/m² on the corresponding days of each subsequent cycle plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle, with or without isatuximab. The antibody was dosed 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 then every 2 weeks thereafter.

Treatments were continued until disease progression, unacceptable toxicity, or patient choice intervened.

At a prespecified interim analysis, the trial met its primary endpoint of a minimum 41% risk reduction in the hazard rate for progression free survival (PFS), with an actual risk reduction of 47%.

An analysis of PFS by subgroup showed significant benefits with the triple combination for patients aged 65 years and older, those with baseline estimated glomerular filtration rates below 60 mL/min per 1.73 m², those with more than one prior line of therapy, those who had not previously received a proteasome inhibitor (e.g., bortezomib) or immunomodulatory agent (e.g., lenalidomide), those with high-risk cytogenetic status, and those with R-ISS stage II at study entry.

Overall response rates were similar between the study arms, at 86.6% with Isa-Kd and 82.9% with Kd, but the rate of very good partial responses or better was significantly higher with the triplet, at 72.6% versus 56.1% (P = .0011). The rate of minimal residual disease negativity was also significantly lower with Isa-Kd in the intent-to-treat population, at 29.6% versus 13%, respectively (P = .0004).

Overall survival data were not mature at the time of data cutoff and will be reported later, Dr. Moreau said.

Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 76.8% of patients on the triplet and 67.2% of those on Kd. The incidences of death, serious TEAEs, or adverse events leading to discontinuation of therapy did not differ markedly between the treatment arms, however. Grade 3 or greater cardiac failure occurred in seven patients treated with the triplet (4%) and five treated with Kd (4.1%); respective rates of grade 3 or greater hematologic abnormalities included anemia in 22% and 19.7%, neutropenia in 19.2% and 7.4%, and thrombocytopenia in 29.9% and 23.8%.

The primary completion date for the trial is estimated to occur in November 2020, with final results in November 2023.

The study was sponsored by Sanofi. Dr. Moreau disclosed honoraria and a consulting or advisory role with several companies, not including Sanofi. Dr. Lipe disclosed impending advisory board activity for Janssen.

SOURCE: Moreau P et al. EHA Congress, Abstract LB2603.

The risk of progression or death for patients with relapsed or refractory multiple myeloma was nearly halved with the addition of isatuximab to carfilzomib and dexamethasone, according to an interim analysis of the phase 3 IKEMA trial (NCT03275285).

After a median follow-up of 20.7 months, the median progression-free survival had not been reached for 179 patients treated with isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (together, known as Isa-Kd), compared with 19.5 months for 123 patients treated with carfilzomib and dexamethasone alone (Kd). The hazard ratio for progression free survival with the triple combination was 0.531 (P = .0007), reported coprincipal investigator Phillipe Moreau, MD, from the University Hospital Hôtel-Dieu in Nantes, France.

“The benefit of the triplet combination was observed across subgroups, including patients difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” he said in a late-breaking abstract presentation during the virtual annual congress of the European Hematology Association.

Isatuximab is an immunoglobulin G1 monoclonal antibody targeting a CD38 transmembrane glycoprotein on multiple myeloma cells, with a mechanism of action similar to that of another anti-CD38 antibody, daratumumab (Darzalex). Isatuximab is approved in the United States and Europe in combination with pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma after at least two prior lines of therapy.
 

A ‘me too’ agent?

It’s unclear, however, whether isatuximab offers any additional benefit over daratumumab, an agent approved for use both in front line therapy combinations and for patients with relapsed/refractory disease, said Brea C. Lipe, MD, a multiple myeloma specialist at the University of Rochester (N.Y.) Wilmot Cancer Institute, who was not involved in the study.

“Every time we get a new drug it’s nice to have another option, but it doesn’t really add anything different from daratumumab at this point,” she said in an interview.

Dr. Lipe noted the IKEMA results are similar to those seen in the phase 3 CANDOR trial, comparing carfilzomib, dexamethasone, and daratumumab to carfilzomib/dexamethasone alone in patients with relapsed/refractory myeloma. In addition, it’s unknown whether patients with disease that is refractory to daratumumab could benefit from isatuximab, she said.

Although isatuximab has been touted as offering more rapid and more convenient dosing than daratumumab, the introduction of rapid infusion and subcutaneous administration of daratumumab has negated any theoretical advantage of the newcomer, Dr. Lipe added.
 

Study details

In the IKEMA trial, 302 patients with relapsed/refractory multiple myeloma who’d received one to three prior lines of therapy were stratified by the number of prior lines and by revised Multiple Myeloma International Staging System (R-ISS) and were then randomized on a 3:2 basis to treatment with carfilzomib 20 mg/m² on days 1, 2, 8, 9, 15, and 16 of cycle 1 and 56 mg/m² on the corresponding days of each subsequent cycle plus dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle, with or without isatuximab. The antibody was dosed 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 then every 2 weeks thereafter.

Treatments were continued until disease progression, unacceptable toxicity, or patient choice intervened.

At a prespecified interim analysis, the trial met its primary endpoint of a minimum 41% risk reduction in the hazard rate for progression free survival (PFS), with an actual risk reduction of 47%.

An analysis of PFS by subgroup showed significant benefits with the triple combination for patients aged 65 years and older, those with baseline estimated glomerular filtration rates below 60 mL/min per 1.73 m², those with more than one prior line of therapy, those who had not previously received a proteasome inhibitor (e.g., bortezomib) or immunomodulatory agent (e.g., lenalidomide), those with high-risk cytogenetic status, and those with R-ISS stage II at study entry.

Overall response rates were similar between the study arms, at 86.6% with Isa-Kd and 82.9% with Kd, but the rate of very good partial responses or better was significantly higher with the triplet, at 72.6% versus 56.1% (P = .0011). The rate of minimal residual disease negativity was also significantly lower with Isa-Kd in the intent-to-treat population, at 29.6% versus 13%, respectively (P = .0004).

Overall survival data were not mature at the time of data cutoff and will be reported later, Dr. Moreau said.

Grade 3 or greater treatment-emergent adverse events (TEAEs) occurred in 76.8% of patients on the triplet and 67.2% of those on Kd. The incidences of death, serious TEAEs, or adverse events leading to discontinuation of therapy did not differ markedly between the treatment arms, however. Grade 3 or greater cardiac failure occurred in seven patients treated with the triplet (4%) and five treated with Kd (4.1%); respective rates of grade 3 or greater hematologic abnormalities included anemia in 22% and 19.7%, neutropenia in 19.2% and 7.4%, and thrombocytopenia in 29.9% and 23.8%.

The primary completion date for the trial is estimated to occur in November 2020, with final results in November 2023.

The study was sponsored by Sanofi. Dr. Moreau disclosed honoraria and a consulting or advisory role with several companies, not including Sanofi. Dr. Lipe disclosed impending advisory board activity for Janssen.

SOURCE: Moreau P et al. EHA Congress, Abstract LB2603.