Multiple Myeloma

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.

Tandem autologous hematopoietic stem cell transplantation (HSCT) could extend progression-free survival (PFS) for some patients with newly diagnosed multiple myeloma, based on long-term data from the phase 3 STaMINA trial.

While the intent-to-treat analysis showed no difference in 6-year PFS rate between single versus tandem HSCT, the as-treated analysis showed that patients who received two transplants had a 6-year PFS rate that was approximately 10% higher than those who received just one transplant, reported lead author Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

The STaMINA trial, also known as BMT CTN 0702, involved 758 patients who were randomized to receive one of three treatment regimens followed by 3 years of maintenance lenalidomide: tandem HSCT (auto/auto), single HSCT plus consolidation with lenalidomide/bortezomib/dexamethasone (auto/RVD), and single HSCT (auto/len).

“At the time, we intended the study to stop approximately 38 months from randomization, allowing for the time for transplant, and then 3 years of maintenance,” Dr. Hari said. However, as the results of lenalidomide maintenance in CALGB 00104 study were reported, they allowed for a follow-on protocol, which provided patients who are progression-free at the completion of the original STaMINA trial to go on to a second follow-on trial, which allowed lenalidomide maintenance on an indefinite basis, he added.

The present analysis looked at the long-term results of this follow-on trial, including the impact of discontinuing lenalidomide.

Aligning with the original study, the present intent-to-treat analysis showed no significant difference between treatment arms for 6-year PFS rate or overall survival. Respectively, PFS rates for auto/auto, auto/RVD, and auto/len were 43.9%, 39.7%, and 40.9% (P = .6).

But 32% of patients in the tandem group never underwent second HSCT, Dr. Hari noted, prompting the as-treated analysis. Although overall survival remained similar between groups, the 6-year PFS was significantly higher for patients who underwent tandem HSCT, at 49.4%, compared with 39.7% for auto/RVD and 38.6% for auto/len (P = .03).

Subgroup analysis showed the statistical benefit of tandem HSCT was driven by high-risk patients, who had a significantly better PFS after tandem transplant, compared with standard-risk patients, who showed no significant benefit.

Dr. Hari called the findings “provocative.”

“The tandem auto approach may still be relevant in high-risk multiple myeloma patients,” he said.

Dr. Hari and his colleagues also found that patients who stayed on maintenance lenalidomide after 38 months had a better 5-year PFS rate than those who discontinued maintenance therapy (79.5% vs. 61%; P = .0004). Subgroup analysis showed this benefit was statistically significant among patients with standard-risk disease (86.3% vs. 66%; P less than .001) but not among those in the high-risk subgroup (86.7% vs. 67.8%; P = .2).

However, Dr. Hari suggested that, based on the similarity of proportions between subgroups, the lack of significance in the high-risk subgroup was likely because of small sample size, suggesting the benefit of maintenance was actually shared across risk strata.

“Lenalidomide maintenance becomes a significant factor for preventing patients from progression,” Dr. Hari said, noting that the tandem transplant approach requires further study, and that he and his colleagues would soon publish minimal residual disease data.

He finished his presentation with a clear clinical recommendation. “Preplanned lenalidomide discontinuation at 3 years is not recommended based on inferior progression-free survival among those who stopped such therapy,” he said.

Invited discussant Joshua R. Richter, MD, of the Icahn School of Medicine at Mount Sinai, New York, said the findings encourage high-dose maintenance therapy, and for some, tandem HSCT.

“The STaMINA study presented today supports the notion that some patients with high-risk disease still may benefit and have further tumor burden reduction with the second transplant that leads to deeper remissions and hopefully abrogates diminished outcomes,” Dr. Richter said during a virtual presentation.

But improvements are needed to better identify such patients, Dr. Richter added. He highlighted a lack of standardization in risk modeling, with various factors currently employed, such as patient characteristics and genomic markers, among several others.

“Better definitions will allow us to cross compare and make true analyses about how to manage these patients,” Dr. Richter said. “Despite the improvements across the board that we’ve seen in myeloma patients, high-risk disease continues to represent a more complicated arena. And patients continue to suffer from worse outcomes, despite all of the other advances.”

The study was funded by the National Institutes of Health. The investigators disclosed additional relationships with Amgen, Celgene, Novartis, and others. Dr. Richter disclosed affiliations with Takeda, Sanofi, Janssen, and others.
 

SOURCE: Hari et al. ASCO 2020. Abstract 8506.

Tandem autologous hematopoietic stem cell transplantation (HSCT) could extend progression-free survival (PFS) for some patients with newly diagnosed multiple myeloma, based on long-term data from the phase 3 STaMINA trial.

While the intent-to-treat analysis showed no difference in 6-year PFS rate between single versus tandem HSCT, the as-treated analysis showed that patients who received two transplants had a 6-year PFS rate that was approximately 10% higher than those who received just one transplant, reported lead author Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

The STaMINA trial, also known as BMT CTN 0702, involved 758 patients who were randomized to receive one of three treatment regimens followed by 3 years of maintenance lenalidomide: tandem HSCT (auto/auto), single HSCT plus consolidation with lenalidomide/bortezomib/dexamethasone (auto/RVD), and single HSCT (auto/len).

“At the time, we intended the study to stop approximately 38 months from randomization, allowing for the time for transplant, and then 3 years of maintenance,” Dr. Hari said. However, as the results of lenalidomide maintenance in CALGB 00104 study were reported, they allowed for a follow-on protocol, which provided patients who are progression-free at the completion of the original STaMINA trial to go on to a second follow-on trial, which allowed lenalidomide maintenance on an indefinite basis, he added.

The present analysis looked at the long-term results of this follow-on trial, including the impact of discontinuing lenalidomide.

Aligning with the original study, the present intent-to-treat analysis showed no significant difference between treatment arms for 6-year PFS rate or overall survival. Respectively, PFS rates for auto/auto, auto/RVD, and auto/len were 43.9%, 39.7%, and 40.9% (P = .6).

But 32% of patients in the tandem group never underwent second HSCT, Dr. Hari noted, prompting the as-treated analysis. Although overall survival remained similar between groups, the 6-year PFS was significantly higher for patients who underwent tandem HSCT, at 49.4%, compared with 39.7% for auto/RVD and 38.6% for auto/len (P = .03).

Subgroup analysis showed the statistical benefit of tandem HSCT was driven by high-risk patients, who had a significantly better PFS after tandem transplant, compared with standard-risk patients, who showed no significant benefit.

Dr. Hari called the findings “provocative.”

“The tandem auto approach may still be relevant in high-risk multiple myeloma patients,” he said.

Dr. Hari and his colleagues also found that patients who stayed on maintenance lenalidomide after 38 months had a better 5-year PFS rate than those who discontinued maintenance therapy (79.5% vs. 61%; P = .0004). Subgroup analysis showed this benefit was statistically significant among patients with standard-risk disease (86.3% vs. 66%; P less than .001) but not among those in the high-risk subgroup (86.7% vs. 67.8%; P = .2).

However, Dr. Hari suggested that, based on the similarity of proportions between subgroups, the lack of significance in the high-risk subgroup was likely because of small sample size, suggesting the benefit of maintenance was actually shared across risk strata.

“Lenalidomide maintenance becomes a significant factor for preventing patients from progression,” Dr. Hari said, noting that the tandem transplant approach requires further study, and that he and his colleagues would soon publish minimal residual disease data.

He finished his presentation with a clear clinical recommendation. “Preplanned lenalidomide discontinuation at 3 years is not recommended based on inferior progression-free survival among those who stopped such therapy,” he said.

Invited discussant Joshua R. Richter, MD, of the Icahn School of Medicine at Mount Sinai, New York, said the findings encourage high-dose maintenance therapy, and for some, tandem HSCT.

“The STaMINA study presented today supports the notion that some patients with high-risk disease still may benefit and have further tumor burden reduction with the second transplant that leads to deeper remissions and hopefully abrogates diminished outcomes,” Dr. Richter said during a virtual presentation.

But improvements are needed to better identify such patients, Dr. Richter added. He highlighted a lack of standardization in risk modeling, with various factors currently employed, such as patient characteristics and genomic markers, among several others.

“Better definitions will allow us to cross compare and make true analyses about how to manage these patients,” Dr. Richter said. “Despite the improvements across the board that we’ve seen in myeloma patients, high-risk disease continues to represent a more complicated arena. And patients continue to suffer from worse outcomes, despite all of the other advances.”

The study was funded by the National Institutes of Health. The investigators disclosed additional relationships with Amgen, Celgene, Novartis, and others. Dr. Richter disclosed affiliations with Takeda, Sanofi, Janssen, and others.
 

SOURCE: Hari et al. ASCO 2020. Abstract 8506.

Tandem autologous hematopoietic stem cell transplantation (HSCT) could extend progression-free survival (PFS) for some patients with newly diagnosed multiple myeloma, based on long-term data from the phase 3 STaMINA trial.

While the intent-to-treat analysis showed no difference in 6-year PFS rate between single versus tandem HSCT, the as-treated analysis showed that patients who received two transplants had a 6-year PFS rate that was approximately 10% higher than those who received just one transplant, reported lead author Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

The STaMINA trial, also known as BMT CTN 0702, involved 758 patients who were randomized to receive one of three treatment regimens followed by 3 years of maintenance lenalidomide: tandem HSCT (auto/auto), single HSCT plus consolidation with lenalidomide/bortezomib/dexamethasone (auto/RVD), and single HSCT (auto/len).

“At the time, we intended the study to stop approximately 38 months from randomization, allowing for the time for transplant, and then 3 years of maintenance,” Dr. Hari said. However, as the results of lenalidomide maintenance in CALGB 00104 study were reported, they allowed for a follow-on protocol, which provided patients who are progression-free at the completion of the original STaMINA trial to go on to a second follow-on trial, which allowed lenalidomide maintenance on an indefinite basis, he added.

The present analysis looked at the long-term results of this follow-on trial, including the impact of discontinuing lenalidomide.

Aligning with the original study, the present intent-to-treat analysis showed no significant difference between treatment arms for 6-year PFS rate or overall survival. Respectively, PFS rates for auto/auto, auto/RVD, and auto/len were 43.9%, 39.7%, and 40.9% (P = .6).

But 32% of patients in the tandem group never underwent second HSCT, Dr. Hari noted, prompting the as-treated analysis. Although overall survival remained similar between groups, the 6-year PFS was significantly higher for patients who underwent tandem HSCT, at 49.4%, compared with 39.7% for auto/RVD and 38.6% for auto/len (P = .03).

Subgroup analysis showed the statistical benefit of tandem HSCT was driven by high-risk patients, who had a significantly better PFS after tandem transplant, compared with standard-risk patients, who showed no significant benefit.

Dr. Hari called the findings “provocative.”

“The tandem auto approach may still be relevant in high-risk multiple myeloma patients,” he said.

Dr. Hari and his colleagues also found that patients who stayed on maintenance lenalidomide after 38 months had a better 5-year PFS rate than those who discontinued maintenance therapy (79.5% vs. 61%; P = .0004). Subgroup analysis showed this benefit was statistically significant among patients with standard-risk disease (86.3% vs. 66%; P less than .001) but not among those in the high-risk subgroup (86.7% vs. 67.8%; P = .2).

However, Dr. Hari suggested that, based on the similarity of proportions between subgroups, the lack of significance in the high-risk subgroup was likely because of small sample size, suggesting the benefit of maintenance was actually shared across risk strata.

“Lenalidomide maintenance becomes a significant factor for preventing patients from progression,” Dr. Hari said, noting that the tandem transplant approach requires further study, and that he and his colleagues would soon publish minimal residual disease data.

He finished his presentation with a clear clinical recommendation. “Preplanned lenalidomide discontinuation at 3 years is not recommended based on inferior progression-free survival among those who stopped such therapy,” he said.

Invited discussant Joshua R. Richter, MD, of the Icahn School of Medicine at Mount Sinai, New York, said the findings encourage high-dose maintenance therapy, and for some, tandem HSCT.

“The STaMINA study presented today supports the notion that some patients with high-risk disease still may benefit and have further tumor burden reduction with the second transplant that leads to deeper remissions and hopefully abrogates diminished outcomes,” Dr. Richter said during a virtual presentation.

But improvements are needed to better identify such patients, Dr. Richter added. He highlighted a lack of standardization in risk modeling, with various factors currently employed, such as patient characteristics and genomic markers, among several others.

“Better definitions will allow us to cross compare and make true analyses about how to manage these patients,” Dr. Richter said. “Despite the improvements across the board that we’ve seen in myeloma patients, high-risk disease continues to represent a more complicated arena. And patients continue to suffer from worse outcomes, despite all of the other advances.”

The study was funded by the National Institutes of Health. The investigators disclosed additional relationships with Amgen, Celgene, Novartis, and others. Dr. Richter disclosed affiliations with Takeda, Sanofi, Janssen, and others.
 

SOURCE: Hari et al. ASCO 2020. Abstract 8506.

Patients with hematological malignancies are at high risk of invasive Staphylococcus pneumoniae. Multiple myeloma (MM) patients, in particular, have been found to have one of the highest incidences of invasive pneumococcal disease. However, researchers found that a full three-dose vaccination regimen by 13-valent pneumococcal conjugate (PCV13) vaccine was protective in MM patients when provided between treatment courses, according to a study reported in Vaccine.

The researchers performed a prospective study of 18 adult patients who were vaccinated with PCV13, compared with 18 control-matched patients from 2017 to 2020. The three-dose vaccination regimen was provided between treatment courses with novel target agents (bortezomib, lenalidomide, ixazomib) with a minimum of a 1-month interval. They used the incidence of pneumonias during the one-year observation period as the primary outcome.

Totally there were 12 cases (33.3%) of clinically and radiologically confirmed pneumonias in the entire study group (n = 36), with a distribution between the vaccinated and nonvaccinated groups of 3 (16.7%) and 9 (50%). respectively (P = .037).

The absolute risk reduction seen with vaccination was 33.3%, and the number needed to treat with PCV13 vaccination in MM patients receiving novel agents was 3.0; (95% confidence interval 1.61-22.1). In addition, there were no adverse effects seen from vaccination, according to the authors.

“Despite the expected decrease in immunological response to vaccination during the chemotherapy, we have shown the clinical effectiveness of a PCV13 vaccination schedule based on 3 doses given with a minimum 1 month interval between the courses of novel agents,” the investigators concluded.

The authors reported that they had no relevant disclosures.
 

[email protected]

SOURCE: Stoma I et al. Vaccine. 2020 May 14; doi.org/10.1016/j.vaccine.2020.05.024.

Patients with hematological malignancies are at high risk of invasive Staphylococcus pneumoniae. Multiple myeloma (MM) patients, in particular, have been found to have one of the highest incidences of invasive pneumococcal disease. However, researchers found that a full three-dose vaccination regimen by 13-valent pneumococcal conjugate (PCV13) vaccine was protective in MM patients when provided between treatment courses, according to a study reported in Vaccine.

The researchers performed a prospective study of 18 adult patients who were vaccinated with PCV13, compared with 18 control-matched patients from 2017 to 2020. The three-dose vaccination regimen was provided between treatment courses with novel target agents (bortezomib, lenalidomide, ixazomib) with a minimum of a 1-month interval. They used the incidence of pneumonias during the one-year observation period as the primary outcome.

Totally there were 12 cases (33.3%) of clinically and radiologically confirmed pneumonias in the entire study group (n = 36), with a distribution between the vaccinated and nonvaccinated groups of 3 (16.7%) and 9 (50%). respectively (P = .037).

The absolute risk reduction seen with vaccination was 33.3%, and the number needed to treat with PCV13 vaccination in MM patients receiving novel agents was 3.0; (95% confidence interval 1.61-22.1). In addition, there were no adverse effects seen from vaccination, according to the authors.

“Despite the expected decrease in immunological response to vaccination during the chemotherapy, we have shown the clinical effectiveness of a PCV13 vaccination schedule based on 3 doses given with a minimum 1 month interval between the courses of novel agents,” the investigators concluded.

The authors reported that they had no relevant disclosures.
 

[email protected]

SOURCE: Stoma I et al. Vaccine. 2020 May 14; doi.org/10.1016/j.vaccine.2020.05.024.

Patients with hematological malignancies are at high risk of invasive Staphylococcus pneumoniae. Multiple myeloma (MM) patients, in particular, have been found to have one of the highest incidences of invasive pneumococcal disease. However, researchers found that a full three-dose vaccination regimen by 13-valent pneumococcal conjugate (PCV13) vaccine was protective in MM patients when provided between treatment courses, according to a study reported in Vaccine.

The researchers performed a prospective study of 18 adult patients who were vaccinated with PCV13, compared with 18 control-matched patients from 2017 to 2020. The three-dose vaccination regimen was provided between treatment courses with novel target agents (bortezomib, lenalidomide, ixazomib) with a minimum of a 1-month interval. They used the incidence of pneumonias during the one-year observation period as the primary outcome.

Totally there were 12 cases (33.3%) of clinically and radiologically confirmed pneumonias in the entire study group (n = 36), with a distribution between the vaccinated and nonvaccinated groups of 3 (16.7%) and 9 (50%). respectively (P = .037).

The absolute risk reduction seen with vaccination was 33.3%, and the number needed to treat with PCV13 vaccination in MM patients receiving novel agents was 3.0; (95% confidence interval 1.61-22.1). In addition, there were no adverse effects seen from vaccination, according to the authors.

“Despite the expected decrease in immunological response to vaccination during the chemotherapy, we have shown the clinical effectiveness of a PCV13 vaccination schedule based on 3 doses given with a minimum 1 month interval between the courses of novel agents,” the investigators concluded.

The authors reported that they had no relevant disclosures.
 

[email protected]

SOURCE: Stoma I et al. Vaccine. 2020 May 14; doi.org/10.1016/j.vaccine.2020.05.024.

While upfront autologous transplantation has bested bortezomib-based intensification therapy in a large, randomized multiple myeloma (MM) trial, investigators and observers say more research will be needed to determine the optimal treatment strategy in the era of novel agents.

Nephron/Wikimedia Commons

Autologous hematopoietic stem cell transplantation (HSCT) extended progression-free survival by almost 15 months compared with bortezomib, melphalan, and prednisone (VMP) intensification therapy for the treatment of newly diagnosed multiple myeloma, according to results of the randomized, phase 3 trial of 1,503 patients enrolled at 172 centers in the European Myeloma Network.

That finding could provide more fodder for the ongoing debate over the role of upfront autologous HSCT as a gold-standard intensification treatment for patients who can tolerate myeloablative doses of chemotherapy in light of the proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies that are now available.

However, the study is not without limitations, including the use of bortezomib, cyclophosphamide, and dexamethasone (VCD) as induction therapy, according to the investigators, led by Michele Cavo, MD, with the Seràgnoli Institute of Hematology at Bologna (Italy) University.

The VCD regimen was one of the most frequently used induction regimens back when the trial was designed, but now it’s considered “less optimal” versus regimens such as bortezomib, lenalidomide, and dexamethasone (VRD), according to Dr. Cavo and coinvestigators.

Besides, the field is moving forward based on clinical trials of “highly active” daratumumab-based four-drug regimens, which appear to enhance rates of response and minimal residual disease (MRD) negativity when given as induction before autologous HSCT and as consolidation afterward, they said.

“Final results from these studies should be awaited before a shift from routine use of upfront autologous HSCT to delayed HSCT or alternative treatment strategies driven by MRD status can be offered to patients with newly diagnosed multiple myeloma who are fit for high-dose chemotherapy,” Dr. Cavo and colleagues noted in their report, available in The Lancet Hematology.

The multicenter, randomized, open-label, phase 3 study by Dr. Cavo and coinvestigators, known as EMN02/HO95, included patients up to 65 years of age with symptomatic multiple myeloma, measurable disease, and WHO performance of 0 to 2. Patients were treated with VCD induction therapy, followed by randomization to either VMP or autologous HSCT after high-dose melphalan. In a second randomization, patients were assigned to either VRD consolidation therapy or no consolidation. All patients then received lenalidomide maintenance therapy until progression.

Median progression-free survival was 56.7 months in patients initially randomized to HSCT, compared with 41.9 months for MP (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P = .0001), according to the investigators, who said that finding supports the value of HSCT “even in the era of highly active novel agents.”

Turning to results of the second randomization, Dr. Cavo and colleagues said the VRD consolidation strategy resulted in median progression-free survival that was significantly improved versus no consolidation, at 58.9 months and 45.5 months, respectively (P = .014).

While this is an important study, the added benefit of HSCT intensification therapy is in question given the high rates of MRD being reported for potent, daratumumab-based four-drug combination regimens, according to a related commentary by Omar Nadeem, MD, and Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“We are entering an era in which novel combinations have shown unprecedented efficacy and future studies with or without HSCT will be needed to answer these key questions,” wrote Dr. Nadeem and Dr. Ghobrial.

Dr. Cavo and colleagues said the estimated 5-year rate of overall survival in EMN02/HO95 was “comparable” between arms, at 75% for the HSCT strategy and 72% for VMP.

“Although this suggests that delaying HSCT to a later time is not harmful, a substantial proportion of patients may become ineligible for high-dose melphalan at first relapse,” they said, noting that 63% of VMP-treated patients went on to receive salvage HSCT.

Further follow-up could demonstrate a survival advantage, as seen in other studies, they added.

Dr. Cavo reported that he has received honoraria from multiple pharmaceutical companies, and is a member of speakers bureaus for Janssen and Celgene. Dr. Nadeem and Dr. Ghobrial reported serving on the advisory boards of multiple pharmaceutical companies.

SOURCE: Cavo M et al. Lancet Haematol. 2020 Apr 30. doi: 10.1016/S2352-3026(20)30099-5.

While upfront autologous transplantation has bested bortezomib-based intensification therapy in a large, randomized multiple myeloma (MM) trial, investigators and observers say more research will be needed to determine the optimal treatment strategy in the era of novel agents.

Nephron/Wikimedia Commons

Autologous hematopoietic stem cell transplantation (HSCT) extended progression-free survival by almost 15 months compared with bortezomib, melphalan, and prednisone (VMP) intensification therapy for the treatment of newly diagnosed multiple myeloma, according to results of the randomized, phase 3 trial of 1,503 patients enrolled at 172 centers in the European Myeloma Network.

That finding could provide more fodder for the ongoing debate over the role of upfront autologous HSCT as a gold-standard intensification treatment for patients who can tolerate myeloablative doses of chemotherapy in light of the proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies that are now available.

However, the study is not without limitations, including the use of bortezomib, cyclophosphamide, and dexamethasone (VCD) as induction therapy, according to the investigators, led by Michele Cavo, MD, with the Seràgnoli Institute of Hematology at Bologna (Italy) University.

The VCD regimen was one of the most frequently used induction regimens back when the trial was designed, but now it’s considered “less optimal” versus regimens such as bortezomib, lenalidomide, and dexamethasone (VRD), according to Dr. Cavo and coinvestigators.

Besides, the field is moving forward based on clinical trials of “highly active” daratumumab-based four-drug regimens, which appear to enhance rates of response and minimal residual disease (MRD) negativity when given as induction before autologous HSCT and as consolidation afterward, they said.

“Final results from these studies should be awaited before a shift from routine use of upfront autologous HSCT to delayed HSCT or alternative treatment strategies driven by MRD status can be offered to patients with newly diagnosed multiple myeloma who are fit for high-dose chemotherapy,” Dr. Cavo and colleagues noted in their report, available in The Lancet Hematology.

The multicenter, randomized, open-label, phase 3 study by Dr. Cavo and coinvestigators, known as EMN02/HO95, included patients up to 65 years of age with symptomatic multiple myeloma, measurable disease, and WHO performance of 0 to 2. Patients were treated with VCD induction therapy, followed by randomization to either VMP or autologous HSCT after high-dose melphalan. In a second randomization, patients were assigned to either VRD consolidation therapy or no consolidation. All patients then received lenalidomide maintenance therapy until progression.

Median progression-free survival was 56.7 months in patients initially randomized to HSCT, compared with 41.9 months for MP (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P = .0001), according to the investigators, who said that finding supports the value of HSCT “even in the era of highly active novel agents.”

Turning to results of the second randomization, Dr. Cavo and colleagues said the VRD consolidation strategy resulted in median progression-free survival that was significantly improved versus no consolidation, at 58.9 months and 45.5 months, respectively (P = .014).

While this is an important study, the added benefit of HSCT intensification therapy is in question given the high rates of MRD being reported for potent, daratumumab-based four-drug combination regimens, according to a related commentary by Omar Nadeem, MD, and Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“We are entering an era in which novel combinations have shown unprecedented efficacy and future studies with or without HSCT will be needed to answer these key questions,” wrote Dr. Nadeem and Dr. Ghobrial.

Dr. Cavo and colleagues said the estimated 5-year rate of overall survival in EMN02/HO95 was “comparable” between arms, at 75% for the HSCT strategy and 72% for VMP.

“Although this suggests that delaying HSCT to a later time is not harmful, a substantial proportion of patients may become ineligible for high-dose melphalan at first relapse,” they said, noting that 63% of VMP-treated patients went on to receive salvage HSCT.

Further follow-up could demonstrate a survival advantage, as seen in other studies, they added.

Dr. Cavo reported that he has received honoraria from multiple pharmaceutical companies, and is a member of speakers bureaus for Janssen and Celgene. Dr. Nadeem and Dr. Ghobrial reported serving on the advisory boards of multiple pharmaceutical companies.

SOURCE: Cavo M et al. Lancet Haematol. 2020 Apr 30. doi: 10.1016/S2352-3026(20)30099-5.

While upfront autologous transplantation has bested bortezomib-based intensification therapy in a large, randomized multiple myeloma (MM) trial, investigators and observers say more research will be needed to determine the optimal treatment strategy in the era of novel agents.

Nephron/Wikimedia Commons

Autologous hematopoietic stem cell transplantation (HSCT) extended progression-free survival by almost 15 months compared with bortezomib, melphalan, and prednisone (VMP) intensification therapy for the treatment of newly diagnosed multiple myeloma, according to results of the randomized, phase 3 trial of 1,503 patients enrolled at 172 centers in the European Myeloma Network.

That finding could provide more fodder for the ongoing debate over the role of upfront autologous HSCT as a gold-standard intensification treatment for patients who can tolerate myeloablative doses of chemotherapy in light of the proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies that are now available.

However, the study is not without limitations, including the use of bortezomib, cyclophosphamide, and dexamethasone (VCD) as induction therapy, according to the investigators, led by Michele Cavo, MD, with the Seràgnoli Institute of Hematology at Bologna (Italy) University.

The VCD regimen was one of the most frequently used induction regimens back when the trial was designed, but now it’s considered “less optimal” versus regimens such as bortezomib, lenalidomide, and dexamethasone (VRD), according to Dr. Cavo and coinvestigators.

Besides, the field is moving forward based on clinical trials of “highly active” daratumumab-based four-drug regimens, which appear to enhance rates of response and minimal residual disease (MRD) negativity when given as induction before autologous HSCT and as consolidation afterward, they said.

“Final results from these studies should be awaited before a shift from routine use of upfront autologous HSCT to delayed HSCT or alternative treatment strategies driven by MRD status can be offered to patients with newly diagnosed multiple myeloma who are fit for high-dose chemotherapy,” Dr. Cavo and colleagues noted in their report, available in The Lancet Hematology.

The multicenter, randomized, open-label, phase 3 study by Dr. Cavo and coinvestigators, known as EMN02/HO95, included patients up to 65 years of age with symptomatic multiple myeloma, measurable disease, and WHO performance of 0 to 2. Patients were treated with VCD induction therapy, followed by randomization to either VMP or autologous HSCT after high-dose melphalan. In a second randomization, patients were assigned to either VRD consolidation therapy or no consolidation. All patients then received lenalidomide maintenance therapy until progression.

Median progression-free survival was 56.7 months in patients initially randomized to HSCT, compared with 41.9 months for MP (hazard ratio, 0.73; 95% confidence interval, 0.62-0.85; P = .0001), according to the investigators, who said that finding supports the value of HSCT “even in the era of highly active novel agents.”

Turning to results of the second randomization, Dr. Cavo and colleagues said the VRD consolidation strategy resulted in median progression-free survival that was significantly improved versus no consolidation, at 58.9 months and 45.5 months, respectively (P = .014).

While this is an important study, the added benefit of HSCT intensification therapy is in question given the high rates of MRD being reported for potent, daratumumab-based four-drug combination regimens, according to a related commentary by Omar Nadeem, MD, and Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.

“We are entering an era in which novel combinations have shown unprecedented efficacy and future studies with or without HSCT will be needed to answer these key questions,” wrote Dr. Nadeem and Dr. Ghobrial.

Dr. Cavo and colleagues said the estimated 5-year rate of overall survival in EMN02/HO95 was “comparable” between arms, at 75% for the HSCT strategy and 72% for VMP.

“Although this suggests that delaying HSCT to a later time is not harmful, a substantial proportion of patients may become ineligible for high-dose melphalan at first relapse,” they said, noting that 63% of VMP-treated patients went on to receive salvage HSCT.

Further follow-up could demonstrate a survival advantage, as seen in other studies, they added.

Dr. Cavo reported that he has received honoraria from multiple pharmaceutical companies, and is a member of speakers bureaus for Janssen and Celgene. Dr. Nadeem and Dr. Ghobrial reported serving on the advisory boards of multiple pharmaceutical companies.

SOURCE: Cavo M et al. Lancet Haematol. 2020 Apr 30. doi: 10.1016/S2352-3026(20)30099-5.

Small phase 1 and phase 2 multi-center, open label studies of melflufen toxicity and efficacy in combination with dexamethasone showed significant benefits in overall response rate in patients with relapsed/refractory multiple myeloma. A report on these studies was published in Lancet Hematology.

Nephron/Wikimedia Commons

In phase 2, patients treated with combination therapy achieved an overall response rate of 31% (14/45 patients) and a clinical benefit rate of 49% (22/45 patients). In the phase 2 single-agent cohort, the overall response rate was 8% (1/13 patients) and the clinical benefit rate was 23% (3/13 patients) before this aspect of the study was discontinued.

In terms of adverse events, among the 45 phase 2 combination–treatment patients, the most common grade 3-4 adverse events were clinically manageable thrombocytopenia (62% of patients) and neutropenia (58%) In addition, 24 serious adverse events were reported in 38% patients, most commonly pneumonia (11%).

Because of the benefits seen and the need for relapsed/refractory MM treatments, further studies on melflufen in combination therapies are ongoing, according to the researchers “with encouraging early results to date”: NCT03151811, NCT02963493, and NCT03481556.

“Melflufen represents a novel treatment concept with a unique mechanism of action that might find future use in combinations with key partners, such as proteasome inhibitors and monoclonal antibodies,” the researchers concluded.

The study was sponsored by Oncopeptides AB. The authors received funding from a variety of pharmaceutical companies.

[email protected]

SOURCE: Richardson PG et al. Lancet Hematol. 2020; doi.org/10.1016/S2352-3026(20)30044-2.

Small phase 1 and phase 2 multi-center, open label studies of melflufen toxicity and efficacy in combination with dexamethasone showed significant benefits in overall response rate in patients with relapsed/refractory multiple myeloma. A report on these studies was published in Lancet Hematology.

Nephron/Wikimedia Commons

In phase 2, patients treated with combination therapy achieved an overall response rate of 31% (14/45 patients) and a clinical benefit rate of 49% (22/45 patients). In the phase 2 single-agent cohort, the overall response rate was 8% (1/13 patients) and the clinical benefit rate was 23% (3/13 patients) before this aspect of the study was discontinued.

In terms of adverse events, among the 45 phase 2 combination–treatment patients, the most common grade 3-4 adverse events were clinically manageable thrombocytopenia (62% of patients) and neutropenia (58%) In addition, 24 serious adverse events were reported in 38% patients, most commonly pneumonia (11%).

Because of the benefits seen and the need for relapsed/refractory MM treatments, further studies on melflufen in combination therapies are ongoing, according to the researchers “with encouraging early results to date”: NCT03151811, NCT02963493, and NCT03481556.

“Melflufen represents a novel treatment concept with a unique mechanism of action that might find future use in combinations with key partners, such as proteasome inhibitors and monoclonal antibodies,” the researchers concluded.

The study was sponsored by Oncopeptides AB. The authors received funding from a variety of pharmaceutical companies.

[email protected]

SOURCE: Richardson PG et al. Lancet Hematol. 2020; doi.org/10.1016/S2352-3026(20)30044-2.

Small phase 1 and phase 2 multi-center, open label studies of melflufen toxicity and efficacy in combination with dexamethasone showed significant benefits in overall response rate in patients with relapsed/refractory multiple myeloma. A report on these studies was published in Lancet Hematology.

Nephron/Wikimedia Commons

In phase 2, patients treated with combination therapy achieved an overall response rate of 31% (14/45 patients) and a clinical benefit rate of 49% (22/45 patients). In the phase 2 single-agent cohort, the overall response rate was 8% (1/13 patients) and the clinical benefit rate was 23% (3/13 patients) before this aspect of the study was discontinued.

In terms of adverse events, among the 45 phase 2 combination–treatment patients, the most common grade 3-4 adverse events were clinically manageable thrombocytopenia (62% of patients) and neutropenia (58%) In addition, 24 serious adverse events were reported in 38% patients, most commonly pneumonia (11%).

Because of the benefits seen and the need for relapsed/refractory MM treatments, further studies on melflufen in combination therapies are ongoing, according to the researchers “with encouraging early results to date”: NCT03151811, NCT02963493, and NCT03481556.

“Melflufen represents a novel treatment concept with a unique mechanism of action that might find future use in combinations with key partners, such as proteasome inhibitors and monoclonal antibodies,” the researchers concluded.

The study was sponsored by Oncopeptides AB. The authors received funding from a variety of pharmaceutical companies.

[email protected]

SOURCE: Richardson PG et al. Lancet Hematol. 2020; doi.org/10.1016/S2352-3026(20)30044-2.

The American Society of Hematology has committed a portion of its website to providing continually updated information addressing specific hematologic disorders in relation to COVID-19.

“As the world grapples with the novel coronavirus, ASH believes that we can help each other be as knowledgeable and prepared as possible,” wrote the society’s president, Stephanie J. Lee, MD, MPH.

On its website, ASH provides relevant COVID-19 information in a series of FAQ divided into malignant and nonmalignant hematologic diseases and disorders. In the malignant category, the various lymphomas and leukemias are individually addressed, as well as other conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. In the nonmalignant category, ASH has provided FAQ on aplastic anemia, thalassemia, sickle cell disease, pulmonary embolism, venous thromboembolism/anticoagulation, coagulopathy, and immune as well as thrombotic thrombocytopenic purpura.

In addition to the continually updated series of relevant FAQ, as part of its response to the pandemic ASH is promoting two unique COVID-19 registries for physicians: the ASH Research Collaborative’s (ASH RC) Data Hub COVID-19 Registry and the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion Sickle Cell Disease (SECURE-SCD) Registry.

“The ASH Research Collaborative’s (ASH RC) Data Hub launched the COVID-19 Registry and is currently capturing data on people who test positive for COVID-19 and have been or are currently being treated for hematologic malignancy,” according to the website. The intention is to provide “near real-time observational data summaries,” which will hopefully provide useful information to clinicians treating hematologic malignancies in patients in the midst of the COVID-19 pandemic.

The registry allows clinicians to enter their own cases in a specified format to allow data analysis on clinical practice and patient outcomes that will be aggregated to provide rapid insights for clinicians to help them care for their patients, according to ASH.

The second registry specifically deals with COVID-19 cases in patients with sickle cell disease. It also allows clinicians to add cases with a similar intention of aggregating data to provide near real-time insights into patient care. “We are asking providers caring for these patients to report all of their cases of COVID-19 to this registry,” according to the registry website. The registry is for reporting COVID-19 cases in sickle cell disease patients “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

ASH also provides more generalized information for hematology practitioners dealing with COVID-19 on the topics of conducting their practice and using telemedicine, among others.

Correction, April 15, 2020: This story originally said incorrectly that ASH developed the 2 new registries. The registries are merely being promoted on the ASH website.

[email protected]

The American Society of Hematology has committed a portion of its website to providing continually updated information addressing specific hematologic disorders in relation to COVID-19.

“As the world grapples with the novel coronavirus, ASH believes that we can help each other be as knowledgeable and prepared as possible,” wrote the society’s president, Stephanie J. Lee, MD, MPH.

On its website, ASH provides relevant COVID-19 information in a series of FAQ divided into malignant and nonmalignant hematologic diseases and disorders. In the malignant category, the various lymphomas and leukemias are individually addressed, as well as other conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. In the nonmalignant category, ASH has provided FAQ on aplastic anemia, thalassemia, sickle cell disease, pulmonary embolism, venous thromboembolism/anticoagulation, coagulopathy, and immune as well as thrombotic thrombocytopenic purpura.

In addition to the continually updated series of relevant FAQ, as part of its response to the pandemic ASH is promoting two unique COVID-19 registries for physicians: the ASH Research Collaborative’s (ASH RC) Data Hub COVID-19 Registry and the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion Sickle Cell Disease (SECURE-SCD) Registry.

“The ASH Research Collaborative’s (ASH RC) Data Hub launched the COVID-19 Registry and is currently capturing data on people who test positive for COVID-19 and have been or are currently being treated for hematologic malignancy,” according to the website. The intention is to provide “near real-time observational data summaries,” which will hopefully provide useful information to clinicians treating hematologic malignancies in patients in the midst of the COVID-19 pandemic.

The registry allows clinicians to enter their own cases in a specified format to allow data analysis on clinical practice and patient outcomes that will be aggregated to provide rapid insights for clinicians to help them care for their patients, according to ASH.

The second registry specifically deals with COVID-19 cases in patients with sickle cell disease. It also allows clinicians to add cases with a similar intention of aggregating data to provide near real-time insights into patient care. “We are asking providers caring for these patients to report all of their cases of COVID-19 to this registry,” according to the registry website. The registry is for reporting COVID-19 cases in sickle cell disease patients “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

ASH also provides more generalized information for hematology practitioners dealing with COVID-19 on the topics of conducting their practice and using telemedicine, among others.

Correction, April 15, 2020: This story originally said incorrectly that ASH developed the 2 new registries. The registries are merely being promoted on the ASH website.

[email protected]

The American Society of Hematology has committed a portion of its website to providing continually updated information addressing specific hematologic disorders in relation to COVID-19.

“As the world grapples with the novel coronavirus, ASH believes that we can help each other be as knowledgeable and prepared as possible,” wrote the society’s president, Stephanie J. Lee, MD, MPH.

On its website, ASH provides relevant COVID-19 information in a series of FAQ divided into malignant and nonmalignant hematologic diseases and disorders. In the malignant category, the various lymphomas and leukemias are individually addressed, as well as other conditions such as myelodysplastic syndromes, myeloproliferative neoplasms, and multiple myeloma. In the nonmalignant category, ASH has provided FAQ on aplastic anemia, thalassemia, sickle cell disease, pulmonary embolism, venous thromboembolism/anticoagulation, coagulopathy, and immune as well as thrombotic thrombocytopenic purpura.

In addition to the continually updated series of relevant FAQ, as part of its response to the pandemic ASH is promoting two unique COVID-19 registries for physicians: the ASH Research Collaborative’s (ASH RC) Data Hub COVID-19 Registry and the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion Sickle Cell Disease (SECURE-SCD) Registry.

“The ASH Research Collaborative’s (ASH RC) Data Hub launched the COVID-19 Registry and is currently capturing data on people who test positive for COVID-19 and have been or are currently being treated for hematologic malignancy,” according to the website. The intention is to provide “near real-time observational data summaries,” which will hopefully provide useful information to clinicians treating hematologic malignancies in patients in the midst of the COVID-19 pandemic.

The registry allows clinicians to enter their own cases in a specified format to allow data analysis on clinical practice and patient outcomes that will be aggregated to provide rapid insights for clinicians to help them care for their patients, according to ASH.

The second registry specifically deals with COVID-19 cases in patients with sickle cell disease. It also allows clinicians to add cases with a similar intention of aggregating data to provide near real-time insights into patient care. “We are asking providers caring for these patients to report all of their cases of COVID-19 to this registry,” according to the registry website. The registry is for reporting COVID-19 cases in sickle cell disease patients “after sufficient time has passed to observe the disease course through resolution of acute illness and/or death.”

ASH also provides more generalized information for hematology practitioners dealing with COVID-19 on the topics of conducting their practice and using telemedicine, among others.

Correction, April 15, 2020: This story originally said incorrectly that ASH developed the 2 new registries. The registries are merely being promoted on the ASH website.

[email protected]