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EC expands approval for daratumumab in MM
The European Commission (EC) has expanded the approved use of the anti-CD38 antibody daratumumab (Darzalex®).
Daratumumab is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of adults with multiple myeloma (MM) who have received at least 1 prior therapy.
The EC previously granted conditional approval for daratumumab as monotherapy for the treatment of adults with relapsed or refractory MM whose prior treatment included a proteasome inhibitor and an immunomodulatory agent and who demonstrated disease progression on their last therapy.
Now, the EC has granted daratumumab full approval for this indication. The conditional approval was contingent upon Janssen, the company developing daratumumab, providing additional data from the phase 3 POLLUX and CASTOR trials.
As these data have been provided, the EC said the specific obligations associated with the conditional approval have been fulfilled, allowing the switch from conditional to full approval.
The EC’s decision to grant daratumumab approval in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone was also based on data from the POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October 2016.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August 2016. 
The European Commission (EC) has expanded the approved use of the anti-CD38 antibody daratumumab (Darzalex®).
Daratumumab is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of adults with multiple myeloma (MM) who have received at least 1 prior therapy.
The EC previously granted conditional approval for daratumumab as monotherapy for the treatment of adults with relapsed or refractory MM whose prior treatment included a proteasome inhibitor and an immunomodulatory agent and who demonstrated disease progression on their last therapy.
Now, the EC has granted daratumumab full approval for this indication. The conditional approval was contingent upon Janssen, the company developing daratumumab, providing additional data from the phase 3 POLLUX and CASTOR trials.
As these data have been provided, the EC said the specific obligations associated with the conditional approval have been fulfilled, allowing the switch from conditional to full approval.
The EC’s decision to grant daratumumab approval in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone was also based on data from the POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October 2016.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August 2016.
The European Commission (EC) has expanded the approved use of the anti-CD38 antibody daratumumab (Darzalex®).
Daratumumab is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone for the treatment of adults with multiple myeloma (MM) who have received at least 1 prior therapy.
The EC previously granted conditional approval for daratumumab as monotherapy for the treatment of adults with relapsed or refractory MM whose prior treatment included a proteasome inhibitor and an immunomodulatory agent and who demonstrated disease progression on their last therapy.
Now, the EC has granted daratumumab full approval for this indication. The conditional approval was contingent upon Janssen, the company developing daratumumab, providing additional data from the phase 3 POLLUX and CASTOR trials.
As these data have been provided, the EC said the specific obligations associated with the conditional approval have been fulfilled, allowing the switch from conditional to full approval.
The EC’s decision to grant daratumumab approval in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone was also based on data from the POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October 2016.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August 2016.
FDA issues warnings about illegal ‘anticancer’ products
The US Food and Drug Administration (FDA) has posted warning letters addressed to 14 US-based companies illegally selling more than 65 products.
The companies are fraudulently claiming that these products prevent, diagnose, treat, or cure cancer.
The products are being marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs.
“We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a healthcare professional about proper prevention, diagnosis, and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate, or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses.
The illegally sold products cited in the FDA’s warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices).
They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anticancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction, and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent cancer-related products on websites, social media, and in stores.
Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due, in part, to the ease with which companies can move their marketing operations to new websites.
The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages healthcare professionals and consumers to report adverse reactions associated with these or similar products to the FDA’s MedWatch program.
The US Food and Drug Administration (FDA) has posted warning letters addressed to 14 US-based companies illegally selling more than 65 products.
The companies are fraudulently claiming that these products prevent, diagnose, treat, or cure cancer.
The products are being marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs.
“We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a healthcare professional about proper prevention, diagnosis, and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate, or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses.
The illegally sold products cited in the FDA’s warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices).
They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anticancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction, and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent cancer-related products on websites, social media, and in stores.
Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due, in part, to the ease with which companies can move their marketing operations to new websites.
The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages healthcare professionals and consumers to report adverse reactions associated with these or similar products to the FDA’s MedWatch program.
The US Food and Drug Administration (FDA) has posted warning letters addressed to 14 US-based companies illegally selling more than 65 products.
The companies are fraudulently claiming that these products prevent, diagnose, treat, or cure cancer.
The products are being marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs.
“We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a healthcare professional about proper prevention, diagnosis, and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate, or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses.
The illegally sold products cited in the FDA’s warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices).
They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anticancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction, and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent cancer-related products on websites, social media, and in stores.
Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due, in part, to the ease with which companies can move their marketing operations to new websites.
The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages healthcare professionals and consumers to report adverse reactions associated with these or similar products to the FDA’s MedWatch program.
A spouse’s cancer diagnosis can lower household income
A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.
Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.
“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.
“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”
One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.
“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”
“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”
The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.
The women had lower average employment rates, so the decrease represented a larger relative decline for them.
When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.
When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.
Total family income decreased by up to 4.8% among men and 8.5% among women.
The investigators found the declines were due to lower earnings among both cancer patients and their spouses.
“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”
“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”
Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.
“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”
A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.
Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.
“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.
“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”
One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.
“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”
“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”
The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.
The women had lower average employment rates, so the decrease represented a larger relative decline for them.
When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.
When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.
Total family income decreased by up to 4.8% among men and 8.5% among women.
The investigators found the declines were due to lower earnings among both cancer patients and their spouses.
“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”
“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”
Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.
“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”
A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.
Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.
“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.
“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”
One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.
“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”
“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”
The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.
The women had lower average employment rates, so the decrease represented a larger relative decline for them.
When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.
When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.
Total family income decreased by up to 4.8% among men and 8.5% among women.
The investigators found the declines were due to lower earnings among both cancer patients and their spouses.
“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”
“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”
Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.
“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”
Lenalidomide maintains posttransplant remissions in myeloma
NEW YORK – Recent trial results have shown the importance of treating patients with multiple myeloma with the immunomodulator lenalidomide for maintaining negative minimal residual disease and sustained complete responses following autologous stem cell transplantation, experts said at a conference held by Imedex.
“How do you keep the therapy pedal to the metal over time? Lenalidomide is easy to deliver, convenient, and improves progression-free survival and overall survival,” said Paul G. Richardson, MD, professor of medicine at Harvard University and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston. “Lenalidomide maintenance is standard of care. It provides a platform on which you can reliably add new agents for maintenance of remission following autologous stem cell transplantation,” in patients with multiple myeloma.
In a meta-analysis of three randomized, controlled trials with 1,208 patients with multiple myeloma who had undergone induction and autologous stem cell transplant, the overall mortality rate dropped by 0.75 (95% CI, 0.63-0.90) among patients maintained on lenalidomide, compared with placebo (J Clin Oncol. 2016;34:suppl;abstract 8001).
A third study that Dr. Richardson cited showed the difficulty of improving on lenalidomide. The BMT CTN 0702 (Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma) trial randomized 758 multiple myeloma patients to three different autologous stem cell transplant regimens, each followed by lenalidomide maintenance. One arm followed the transplant with four cycles of consolidation therapy with lenalidomide, dexamethasone, and bortezomib (Velcade); one arm used two tandem transplantations; and the third arm used a single transplantation. All three arms had similar rates of progression-free survival and overall survival during follow-up (Blood. 2016 Dec 6;LBA-1). The results showed that “lenalidomide maintenance is an equalizer,” Dr. Richardson said.
She cited a U.S., multicenter, phase II study that followed 66 newly diagnosed patients with multiple myeloma who proceeded through induction, autologous stem cell transplantation, and multiple cycles of consolidation therapy with a regimen of lenalidomide, the proteasome inhibitor carfilzomib (Kyprolis), and dexamethasone. Fifty patients went through 18 cycles of this consolidation regimen and showed an 84% rate of stringent complete response, “the first time we’ve seen such results,” said Dr. Lentzsch, director of the Multiple Myeloma and Amyloidosis Program at Columbia University in New York. “This translated into an excellent” progression-free survival of 86% after 3 years and an overall survival of 95% after 3 years (Blood. 2016 Dec 5;Abstract 675). “I’m pretty impressed” by the results, she added.
An advantage of the combined regimen used in this study is that it is “relatively well tolerated,” as well as effective for keeping patients in remission, Dr. Lentzsch said. However, she highlighted that this was a small study, so its treatment implications are limited for the time being. “For high-risk patients, use the full combination. For everyone else, we need to wait for results from a randomized, controlled trial,” she advised.
Dr. Richardson has been a consultant to Celgene, the company that markets lenalidomide, and is also a consultant to Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Lentzsch has been a consultant to Amgen, Bristol-Myers Squibb, and Caelum Biosciences.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Recent trial results have shown the importance of treating patients with multiple myeloma with the immunomodulator lenalidomide for maintaining negative minimal residual disease and sustained complete responses following autologous stem cell transplantation, experts said at a conference held by Imedex.
“How do you keep the therapy pedal to the metal over time? Lenalidomide is easy to deliver, convenient, and improves progression-free survival and overall survival,” said Paul G. Richardson, MD, professor of medicine at Harvard University and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston. “Lenalidomide maintenance is standard of care. It provides a platform on which you can reliably add new agents for maintenance of remission following autologous stem cell transplantation,” in patients with multiple myeloma.
In a meta-analysis of three randomized, controlled trials with 1,208 patients with multiple myeloma who had undergone induction and autologous stem cell transplant, the overall mortality rate dropped by 0.75 (95% CI, 0.63-0.90) among patients maintained on lenalidomide, compared with placebo (J Clin Oncol. 2016;34:suppl;abstract 8001).
A third study that Dr. Richardson cited showed the difficulty of improving on lenalidomide. The BMT CTN 0702 (Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma) trial randomized 758 multiple myeloma patients to three different autologous stem cell transplant regimens, each followed by lenalidomide maintenance. One arm followed the transplant with four cycles of consolidation therapy with lenalidomide, dexamethasone, and bortezomib (Velcade); one arm used two tandem transplantations; and the third arm used a single transplantation. All three arms had similar rates of progression-free survival and overall survival during follow-up (Blood. 2016 Dec 6;LBA-1). The results showed that “lenalidomide maintenance is an equalizer,” Dr. Richardson said.
She cited a U.S., multicenter, phase II study that followed 66 newly diagnosed patients with multiple myeloma who proceeded through induction, autologous stem cell transplantation, and multiple cycles of consolidation therapy with a regimen of lenalidomide, the proteasome inhibitor carfilzomib (Kyprolis), and dexamethasone. Fifty patients went through 18 cycles of this consolidation regimen and showed an 84% rate of stringent complete response, “the first time we’ve seen such results,” said Dr. Lentzsch, director of the Multiple Myeloma and Amyloidosis Program at Columbia University in New York. “This translated into an excellent” progression-free survival of 86% after 3 years and an overall survival of 95% after 3 years (Blood. 2016 Dec 5;Abstract 675). “I’m pretty impressed” by the results, she added.
An advantage of the combined regimen used in this study is that it is “relatively well tolerated,” as well as effective for keeping patients in remission, Dr. Lentzsch said. However, she highlighted that this was a small study, so its treatment implications are limited for the time being. “For high-risk patients, use the full combination. For everyone else, we need to wait for results from a randomized, controlled trial,” she advised.
Dr. Richardson has been a consultant to Celgene, the company that markets lenalidomide, and is also a consultant to Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Lentzsch has been a consultant to Amgen, Bristol-Myers Squibb, and Caelum Biosciences.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Recent trial results have shown the importance of treating patients with multiple myeloma with the immunomodulator lenalidomide for maintaining negative minimal residual disease and sustained complete responses following autologous stem cell transplantation, experts said at a conference held by Imedex.
“How do you keep the therapy pedal to the metal over time? Lenalidomide is easy to deliver, convenient, and improves progression-free survival and overall survival,” said Paul G. Richardson, MD, professor of medicine at Harvard University and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston. “Lenalidomide maintenance is standard of care. It provides a platform on which you can reliably add new agents for maintenance of remission following autologous stem cell transplantation,” in patients with multiple myeloma.
In a meta-analysis of three randomized, controlled trials with 1,208 patients with multiple myeloma who had undergone induction and autologous stem cell transplant, the overall mortality rate dropped by 0.75 (95% CI, 0.63-0.90) among patients maintained on lenalidomide, compared with placebo (J Clin Oncol. 2016;34:suppl;abstract 8001).
A third study that Dr. Richardson cited showed the difficulty of improving on lenalidomide. The BMT CTN 0702 (Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma) trial randomized 758 multiple myeloma patients to three different autologous stem cell transplant regimens, each followed by lenalidomide maintenance. One arm followed the transplant with four cycles of consolidation therapy with lenalidomide, dexamethasone, and bortezomib (Velcade); one arm used two tandem transplantations; and the third arm used a single transplantation. All three arms had similar rates of progression-free survival and overall survival during follow-up (Blood. 2016 Dec 6;LBA-1). The results showed that “lenalidomide maintenance is an equalizer,” Dr. Richardson said.
She cited a U.S., multicenter, phase II study that followed 66 newly diagnosed patients with multiple myeloma who proceeded through induction, autologous stem cell transplantation, and multiple cycles of consolidation therapy with a regimen of lenalidomide, the proteasome inhibitor carfilzomib (Kyprolis), and dexamethasone. Fifty patients went through 18 cycles of this consolidation regimen and showed an 84% rate of stringent complete response, “the first time we’ve seen such results,” said Dr. Lentzsch, director of the Multiple Myeloma and Amyloidosis Program at Columbia University in New York. “This translated into an excellent” progression-free survival of 86% after 3 years and an overall survival of 95% after 3 years (Blood. 2016 Dec 5;Abstract 675). “I’m pretty impressed” by the results, she added.
An advantage of the combined regimen used in this study is that it is “relatively well tolerated,” as well as effective for keeping patients in remission, Dr. Lentzsch said. However, she highlighted that this was a small study, so its treatment implications are limited for the time being. “For high-risk patients, use the full combination. For everyone else, we need to wait for results from a randomized, controlled trial,” she advised.
Dr. Richardson has been a consultant to Celgene, the company that markets lenalidomide, and is also a consultant to Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Lentzsch has been a consultant to Amgen, Bristol-Myers Squibb, and Caelum Biosciences.
[email protected]
On Twitter @mitchelzoler
Health Canada expands approval of daratumumab in MM
The drug is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least 1 prior therapy.
Health Canada granted daratumumab priority review for this indication due to a high unmet medical need in patients with MM.
When a drug is granted priority review, Health Canada aims to complete its review of the drug within 180 days from the time an application is submitted.
Health Canada grants priority review to products intended for the treatment, prevention, or diagnosis of serious, life-threatening, or severely debilitating diseases or conditions.
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.
The drug is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.
Daratumumab received conditional approval in Canada last year.
In June 2016, Health Canada issued a Notice of Compliance with Conditions approving daratumumab for MM patients who had received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent.
Phase 3 trial data
Health Canada’s expanded approval for daratumumab is based on data from the phase 3 POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October 2016.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August 2016.
The drug is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least 1 prior therapy.
Health Canada granted daratumumab priority review for this indication due to a high unmet medical need in patients with MM.
When a drug is granted priority review, Health Canada aims to complete its review of the drug within 180 days from the time an application is submitted.
Health Canada grants priority review to products intended for the treatment, prevention, or diagnosis of serious, life-threatening, or severely debilitating diseases or conditions.
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.
The drug is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.
Daratumumab received conditional approval in Canada last year.
In June 2016, Health Canada issued a Notice of Compliance with Conditions approving daratumumab for MM patients who had received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent.
Phase 3 trial data
Health Canada’s expanded approval for daratumumab is based on data from the phase 3 POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October 2016.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August 2016.
The drug is now approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone to treat MM patients who have received at least 1 prior therapy.
Health Canada granted daratumumab priority review for this indication due to a high unmet medical need in patients with MM.
When a drug is granted priority review, Health Canada aims to complete its review of the drug within 180 days from the time an application is submitted.
Health Canada grants priority review to products intended for the treatment, prevention, or diagnosis of serious, life-threatening, or severely debilitating diseases or conditions.
About daratumumab
Daratumumab is a human IgG1k monoclonal antibody that binds to CD38, which is highly expressed on the surface of MM cells.
The drug is being developed by Janssen Biotech, Inc. under an exclusive worldwide license from Genmab.
Daratumumab received conditional approval in Canada last year.
In June 2016, Health Canada issued a Notice of Compliance with Conditions approving daratumumab for MM patients who had received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent.
Phase 3 trial data
Health Canada’s expanded approval for daratumumab is based on data from the phase 3 POLLUX and CASTOR trials.
In the POLLUX trial, researchers compared treatment with lenalidomide and dexamethasone to treatment with daratumumab, lenalidomide, and dexamethasone in patients with relapsed or refractory MM.
Patients who received daratumumab in combination had a significantly higher response rate and longer progression-free survival than patients who received the 2-drug combination.
However, treatment with daratumumab was associated with infusion-related reactions and a higher incidence of neutropenia.
Results from this trial were published in NEJM in October 2016.
In the CASTOR trial, researchers compared treatment with bortezomib and dexamethasone to treatment with daratumumab, bortezomib, and dexamethasone in patients with previously treated MM.
Patients who received the 3-drug combination had a higher response rate, longer progression-free survival, and a higher incidence of grade 3/4 adverse events than those who received the 2-drug combination.
Results from this trial were published in NEJM in August 2016.
Inhibitor exhibits activity against hematologic malignancies
A dual kinase inhibitor is active against a range of hematologic malignancies, according to preclinical research.
Investigators found that ASN002, a SYK/JAK inhibitor, exhibited “potent” antiproliferative activity in leukemia, lymphoma, and myeloma cell lines.
ASN002 also inhibited tumor growth in mouse models of these malignancies and proved active against ibrutinib-resistant diffuse large B-cell lymphoma (DLBCL).
The investigators presented these results at the AACR Annual Meeting 2017 (abstract 4204).
The work was conducted by employees of Asana BioSciences, the company developing ASN002.
The investigators tested ASN002 in 178 cell lines and found the drug exhibited “strong antiproliferative activity” in a range of hematologic cancer cell lines, including:
- Leukemia—HEL31, HL60, Jurkat, MOLM-13, and MOLM-16
- Lymphoma—KARPAS-299, OCI-LY10, OCI-LY-19, Pfeiffer, Raji, Ramos, SU-DHL-1, SU-DHL-6, and SU-DHL-10
- Myeloma—H929, JJN3, OPM2, and U266.
In addition, ASN002 was active against ibrutinib-resistant clones derived from the DLBCL cell line SU-DHL-6.
In a SU-DHL-6 xenograft model, the combination of ASN002 and ibrutinib was more effective than either compound alone.
The investigators also found that ASN002 alone demonstrated “strong tumor growth inhibition” in mouse models of DLBCL (Pfeiffer and SU-DHL-6), myeloma (H929), and erythroleukemia (HEL).
The team pointed out that ASN002 is currently under investigation in a phase 1/2 study of patients with B-cell lymphomas (DLBCL, mantle cell lymphoma, and follicular lymphoma) as well as solid tumors.
The investigators said that, to date, ASN002 has been well tolerated and has shown encouraging early evidence of clinical activity and symptomatic benefit in the lymphoma patients.
A dual kinase inhibitor is active against a range of hematologic malignancies, according to preclinical research.
Investigators found that ASN002, a SYK/JAK inhibitor, exhibited “potent” antiproliferative activity in leukemia, lymphoma, and myeloma cell lines.
ASN002 also inhibited tumor growth in mouse models of these malignancies and proved active against ibrutinib-resistant diffuse large B-cell lymphoma (DLBCL).
The investigators presented these results at the AACR Annual Meeting 2017 (abstract 4204).
The work was conducted by employees of Asana BioSciences, the company developing ASN002.
The investigators tested ASN002 in 178 cell lines and found the drug exhibited “strong antiproliferative activity” in a range of hematologic cancer cell lines, including:
- Leukemia—HEL31, HL60, Jurkat, MOLM-13, and MOLM-16
- Lymphoma—KARPAS-299, OCI-LY10, OCI-LY-19, Pfeiffer, Raji, Ramos, SU-DHL-1, SU-DHL-6, and SU-DHL-10
- Myeloma—H929, JJN3, OPM2, and U266.
In addition, ASN002 was active against ibrutinib-resistant clones derived from the DLBCL cell line SU-DHL-6.
In a SU-DHL-6 xenograft model, the combination of ASN002 and ibrutinib was more effective than either compound alone.
The investigators also found that ASN002 alone demonstrated “strong tumor growth inhibition” in mouse models of DLBCL (Pfeiffer and SU-DHL-6), myeloma (H929), and erythroleukemia (HEL).
The team pointed out that ASN002 is currently under investigation in a phase 1/2 study of patients with B-cell lymphomas (DLBCL, mantle cell lymphoma, and follicular lymphoma) as well as solid tumors.
The investigators said that, to date, ASN002 has been well tolerated and has shown encouraging early evidence of clinical activity and symptomatic benefit in the lymphoma patients.
A dual kinase inhibitor is active against a range of hematologic malignancies, according to preclinical research.
Investigators found that ASN002, a SYK/JAK inhibitor, exhibited “potent” antiproliferative activity in leukemia, lymphoma, and myeloma cell lines.
ASN002 also inhibited tumor growth in mouse models of these malignancies and proved active against ibrutinib-resistant diffuse large B-cell lymphoma (DLBCL).
The investigators presented these results at the AACR Annual Meeting 2017 (abstract 4204).
The work was conducted by employees of Asana BioSciences, the company developing ASN002.
The investigators tested ASN002 in 178 cell lines and found the drug exhibited “strong antiproliferative activity” in a range of hematologic cancer cell lines, including:
- Leukemia—HEL31, HL60, Jurkat, MOLM-13, and MOLM-16
- Lymphoma—KARPAS-299, OCI-LY10, OCI-LY-19, Pfeiffer, Raji, Ramos, SU-DHL-1, SU-DHL-6, and SU-DHL-10
- Myeloma—H929, JJN3, OPM2, and U266.
In addition, ASN002 was active against ibrutinib-resistant clones derived from the DLBCL cell line SU-DHL-6.
In a SU-DHL-6 xenograft model, the combination of ASN002 and ibrutinib was more effective than either compound alone.
The investigators also found that ASN002 alone demonstrated “strong tumor growth inhibition” in mouse models of DLBCL (Pfeiffer and SU-DHL-6), myeloma (H929), and erythroleukemia (HEL).
The team pointed out that ASN002 is currently under investigation in a phase 1/2 study of patients with B-cell lymphomas (DLBCL, mantle cell lymphoma, and follicular lymphoma) as well as solid tumors.
The investigators said that, to date, ASN002 has been well tolerated and has shown encouraging early evidence of clinical activity and symptomatic benefit in the lymphoma patients.
Minimal residual disease eyed for myeloma management
NEW YORK – Testing for minimal residual disease is clearly the state-of-the-art way to gauge the status of treated patients with multiple myeloma, agreed experts. The issue now is whether reliance on MRD to guide management remains investigational or ready for routine practice.
Paul G. Richardson, MD, gave MRD full endorsement as the wave of the future, but cautioned against routine use right now. “MRD is an exciting new tool [but] is not yet the standard of care for routine practice,” he said at the conference held by Imedex.
He cited results from a recent meta-analysis that included data from 14 studies of multiple myeloma patients that examined the correlation of MRD status with progression-free survival and 12 studies that addressed how MRD related to overall survival. The meta-analysis results showed that, among patients in complete remission, the average duration of progression-free survival was 56 months in patients who began follow-up without detectable MRD and 34 months in patients with detectable MRD (JAMA Oncology. 2017 Jan;3[1]:28-35). The average duration of overall survival was 112 months in patients with undetectable MRD and 82 months in those with detectable MRD.
But MRD assessment still has several limitations. Evaluations of its strength for prognosis have largely been based on flow cytometry measures of MRD, an approach recently eclipsed by next-generation sequencing and polymerase chain reaction–based assays. Lack of standardization across the multiple tests now available is another hindrance. In addition, undetectable MRD in a myeloma patient in no way means that the malignancy is gone and that treatment can stop. Patients with undetectable MRD may have better medium-term outcomes, compared with patients with detectable MRD, but even patients with undetectable multiple myeloma still succumb to disease progression several years later.
“Patients negative for MRD do better than patients with detectable MRD, but they still relapse and die. You must maintain treatment in patients negative for MRD,” Dr. Richardson said. The clinical experience “supports the idea that, going forward, MRD has real potential, but MRD is not yet standard of care for routine practice,” he said.
In late 2015, Memorial Sloan-Kettering Cancer Center began routinely using MRD to assess multiple myeloma patients, said C. Ola Landgren, MD, PhD, professor of medicine at Weill Cornell Medical College and chief of the Myeloma Service at Memorial Sloan-Kettering.
He and his associates focus on newly diagnosed multiple myeloma patients who have undergone induction therapy. Patients who come out of the regimen with an undetectable level of MRD at a sensitivity of one cell in a million have the option of receiving high-dose melphalan (Alkeran) followed by autologous stem cell transplantation or maintenance therapy with lenalidomide (Revlimid). Patients who finish induction with detectable MRD can either receive immediate treatment with high-dose melphalan followed by autologous stem cell transplantation or further combination treatment with lenalidomide, carfilzomib (Kyprolis), and dexamethasone, then followed by melphalan and stem cell transplantation (Bone Marrow Transplantation. 2016 July;51[7]:913-4).
“The data show that patients who become MRD negative have longer progression-free survival and overall survival, and we find that more and more patients achieve a MRD-negative state,” said Dr. Landgren. “In our practice, it’s about half of newly diagnosed patients. I think that achieving MRD negativity is more important than the specific treatment a patient receives” for predicting prognosis, he said.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Landgren has been a consultant to Amgen and Takeda and a speaker on behalf of Plexus.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Testing for minimal residual disease is clearly the state-of-the-art way to gauge the status of treated patients with multiple myeloma, agreed experts. The issue now is whether reliance on MRD to guide management remains investigational or ready for routine practice.
Paul G. Richardson, MD, gave MRD full endorsement as the wave of the future, but cautioned against routine use right now. “MRD is an exciting new tool [but] is not yet the standard of care for routine practice,” he said at the conference held by Imedex.
He cited results from a recent meta-analysis that included data from 14 studies of multiple myeloma patients that examined the correlation of MRD status with progression-free survival and 12 studies that addressed how MRD related to overall survival. The meta-analysis results showed that, among patients in complete remission, the average duration of progression-free survival was 56 months in patients who began follow-up without detectable MRD and 34 months in patients with detectable MRD (JAMA Oncology. 2017 Jan;3[1]:28-35). The average duration of overall survival was 112 months in patients with undetectable MRD and 82 months in those with detectable MRD.
But MRD assessment still has several limitations. Evaluations of its strength for prognosis have largely been based on flow cytometry measures of MRD, an approach recently eclipsed by next-generation sequencing and polymerase chain reaction–based assays. Lack of standardization across the multiple tests now available is another hindrance. In addition, undetectable MRD in a myeloma patient in no way means that the malignancy is gone and that treatment can stop. Patients with undetectable MRD may have better medium-term outcomes, compared with patients with detectable MRD, but even patients with undetectable multiple myeloma still succumb to disease progression several years later.
“Patients negative for MRD do better than patients with detectable MRD, but they still relapse and die. You must maintain treatment in patients negative for MRD,” Dr. Richardson said. The clinical experience “supports the idea that, going forward, MRD has real potential, but MRD is not yet standard of care for routine practice,” he said.
In late 2015, Memorial Sloan-Kettering Cancer Center began routinely using MRD to assess multiple myeloma patients, said C. Ola Landgren, MD, PhD, professor of medicine at Weill Cornell Medical College and chief of the Myeloma Service at Memorial Sloan-Kettering.
He and his associates focus on newly diagnosed multiple myeloma patients who have undergone induction therapy. Patients who come out of the regimen with an undetectable level of MRD at a sensitivity of one cell in a million have the option of receiving high-dose melphalan (Alkeran) followed by autologous stem cell transplantation or maintenance therapy with lenalidomide (Revlimid). Patients who finish induction with detectable MRD can either receive immediate treatment with high-dose melphalan followed by autologous stem cell transplantation or further combination treatment with lenalidomide, carfilzomib (Kyprolis), and dexamethasone, then followed by melphalan and stem cell transplantation (Bone Marrow Transplantation. 2016 July;51[7]:913-4).
“The data show that patients who become MRD negative have longer progression-free survival and overall survival, and we find that more and more patients achieve a MRD-negative state,” said Dr. Landgren. “In our practice, it’s about half of newly diagnosed patients. I think that achieving MRD negativity is more important than the specific treatment a patient receives” for predicting prognosis, he said.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Landgren has been a consultant to Amgen and Takeda and a speaker on behalf of Plexus.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Testing for minimal residual disease is clearly the state-of-the-art way to gauge the status of treated patients with multiple myeloma, agreed experts. The issue now is whether reliance on MRD to guide management remains investigational or ready for routine practice.
Paul G. Richardson, MD, gave MRD full endorsement as the wave of the future, but cautioned against routine use right now. “MRD is an exciting new tool [but] is not yet the standard of care for routine practice,” he said at the conference held by Imedex.
He cited results from a recent meta-analysis that included data from 14 studies of multiple myeloma patients that examined the correlation of MRD status with progression-free survival and 12 studies that addressed how MRD related to overall survival. The meta-analysis results showed that, among patients in complete remission, the average duration of progression-free survival was 56 months in patients who began follow-up without detectable MRD and 34 months in patients with detectable MRD (JAMA Oncology. 2017 Jan;3[1]:28-35). The average duration of overall survival was 112 months in patients with undetectable MRD and 82 months in those with detectable MRD.
But MRD assessment still has several limitations. Evaluations of its strength for prognosis have largely been based on flow cytometry measures of MRD, an approach recently eclipsed by next-generation sequencing and polymerase chain reaction–based assays. Lack of standardization across the multiple tests now available is another hindrance. In addition, undetectable MRD in a myeloma patient in no way means that the malignancy is gone and that treatment can stop. Patients with undetectable MRD may have better medium-term outcomes, compared with patients with detectable MRD, but even patients with undetectable multiple myeloma still succumb to disease progression several years later.
“Patients negative for MRD do better than patients with detectable MRD, but they still relapse and die. You must maintain treatment in patients negative for MRD,” Dr. Richardson said. The clinical experience “supports the idea that, going forward, MRD has real potential, but MRD is not yet standard of care for routine practice,” he said.
In late 2015, Memorial Sloan-Kettering Cancer Center began routinely using MRD to assess multiple myeloma patients, said C. Ola Landgren, MD, PhD, professor of medicine at Weill Cornell Medical College and chief of the Myeloma Service at Memorial Sloan-Kettering.
He and his associates focus on newly diagnosed multiple myeloma patients who have undergone induction therapy. Patients who come out of the regimen with an undetectable level of MRD at a sensitivity of one cell in a million have the option of receiving high-dose melphalan (Alkeran) followed by autologous stem cell transplantation or maintenance therapy with lenalidomide (Revlimid). Patients who finish induction with detectable MRD can either receive immediate treatment with high-dose melphalan followed by autologous stem cell transplantation or further combination treatment with lenalidomide, carfilzomib (Kyprolis), and dexamethasone, then followed by melphalan and stem cell transplantation (Bone Marrow Transplantation. 2016 July;51[7]:913-4).
“The data show that patients who become MRD negative have longer progression-free survival and overall survival, and we find that more and more patients achieve a MRD-negative state,” said Dr. Landgren. “In our practice, it’s about half of newly diagnosed patients. I think that achieving MRD negativity is more important than the specific treatment a patient receives” for predicting prognosis, he said.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Landgren has been a consultant to Amgen and Takeda and a speaker on behalf of Plexus.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
Expanded drug combinations produce best myeloma induction
NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.
He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.
“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.
He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.
For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.
Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).
Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.
He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.
“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.
He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.
For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.
Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).
Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.
[email protected]
On Twitter @mitchelzoler
NEW YORK – Optimal induction therapy for patients with multiple myeloma requires all the therapeutic tools currently available for combination therapy, which means using four agents followed by autologous stem cell transplantation, Paul G. Richardson, MD, said at a conference held by Imedex.
He suggested that a rational combination regimen for induction therapy of multiple myeloma would include a second- or third-generation immunomodulator such as lenalidomide (Revlimid) or pomalidomide (Pomalyst); a proteasome inhibitor such as bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro); plus standard dexamethasone to form a contemporary backbone regimen for inducing remission in patients with multiple myeloma.
“Therapeutic parsimony is not recommended. You need a combination” of all available drug classes, suggested Dr. Richardson, professor of medicine at Harvard Medical School and clinical program leader of the Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
“It isn’t rational to limit the treatment choices. We need to bring them all together,” he said. The “most rational” combination melds an immunomodulator, proteasome inhibitor, plus a monoclonal antibody that he called a “true game changer. Add the antibody on top of the three-drug platform” of an immunomodulator, proteasome inhibitor, and dexamethasone. Dr. Richardson conceded, however, that a concern with such combinations is how to manage the toxicity that would likely result.
He cited several recent examples of demonstrated superior efficacy in the form of more complete responses from combined regimens, followed by autologous stem cell transplantation.
For example, a recent report from a French-led group compared the efficacy of a combination of an immunomodulator, proteasome inhibitor, and dexamethasone against the same combination, followed by autologous stem cell transplantation (N Engl J Med. 2017 Apr 6;376[14]:1311-20). The combined regimen plus transplant resulted in a 59% complete response rate, “the best response rate we’ve ever seen” in multiple myeloma, Dr. Richardson noted, compared with a 48% complete response rate in patients who did not undergo a stem cell transplant.
Another speaker at the meeting, Ruben Niesvizky, MD, suggested a more cautious approach to using the monoclonal antibody daratumumab for induction. He cited the published experience in adding the antibody to pared-down backbone therapy in the setting of relapsed or relapsed and refractory disease, such as a proteasome inhibitor plus dexamethasone (N Engl J Med. 2016 Aug 25;375[8]:754-66) or an immunomodulator plus dexamethasone (N Engl J Med. 2016 Oct 6;375[14]:1319-31).
Adding a monoclonal antibody such as daratumumab to combination therapy is the “wave of the future,” said Dr. Niesvizky, professor of medicine and director of the Multiple Myeloma Center at New York Presbyterian Hospital/Weill Cornell Medical Center. It provides treatment that reduces disease-related complications and achieves effective and extended disease control with improved overall survival, while being well tolerated and facilitating stem cell collection.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides AB, and Takeda and has received research funding from Celgene and Takeda. Dr. Niesvizky has been a consultant to Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda and has received research support from Amgen, Bristol-Myers Squibb, Celgene, and Takeda.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
CAR T-cell therapy demonstrates efficacy in mice with MM
WASHINGTON, DC—A chimeric antigen receptor (CAR) T-cell therapy is active against multiple myeloma (MM), according to preclinical research.
The therapy, known as P-BCMA-101, demonstrated persistent anti-tumor activity in a mouse model of MM.
Treatment with P-BCMA-101 eliminated tumors after relapse and prolonged survival in the mice, when compared to other CAR-T cell therapies.
These results were presented in a poster at the AACR Annual Meeting 2017 (abstract 3759).
The research was conducted by employees of Poseida Therapeutics Inc., the company developing P-BCMA-101, as well as others.
About P-BCMA-101
The researchers explained that P-BCMA-101 employs a B-cell maturation antigen (BCMA)-specific Centyrin™ rather than a single-chain variable fragment (scFv) for antigen detection.
Centyrins™ are fully human and have similar binding affinities as scFvs. However, Centyrins are smaller, more thermostable, and predicted to be less immunogenic.
P-BCMA-101 is engineered using the PiggyBac™ DNA modification system. PiggyBac eliminates the need to use lentivirus or gamma-retrovirus as a gene delivery mechanism, resulting in improved manufacturing and cost savings.
In addition, the increased cargo capacity of PiggyBac allows for the incorporation of a safety switch and a selectable gene. The safety switch can be “flipped” to enable depletion in case adverse events occur. And the selectable gene allows for enrichment of CARTyrin+ cells using a non-genotoxic drug.
Findings
The researchers found that more than 70% of P-BCMA-101 cells possessed a stem cell memory phenotype, creating a significant population of self-renewing, multipotent progenitors capable of reconstituting the entire spectrum of memory and effector T-cell subsets required to prevent cancer relapse. Similar competitor products typically report 0% to 20% stem cell memory phenotype.
In addition, P-BCMA-101 was enriched with more than 95% of T cells successfully modified, which compares favorably to the roughly 30% to 50% commonly expected with clinical manufacture using lentivirus.
P-BCMA-101 did not exhibit effects of CAR-mediated tonic signaling, a common cause of T-cell exhaustion that leads to poor durability. Tonic signaling is caused by oligomerization of unstable binding domains commonly seen with traditional scFv CARs.
The researchers tested P-BCMA-101 in NSG mice bearing luciferase+ MM.1S cells. The mice received a single administration of either 4 x 106 or 12 x 106 P-BCMA-101 cells.
P-BCMA-101 treatment reduced tumor burden to the limit of detection within 7 days. Conversely, all untreated control mice succumbed to MM within 4 weeks.
P-BCMA-101 expanded and persisted in the treated mice, eliminated tumors following relapse, and prolonged survival.
Most treated mice survived 110 days, and none of them died from tumor burden during the study. This compares favorably to lentivirus-based products that have shown roughly 50-day survival in the same model.
Based on these results, Poseida plans to initiate a phase 1 trial of P-BCMA-101 in patients with relapsed or refractory MM.
WASHINGTON, DC—A chimeric antigen receptor (CAR) T-cell therapy is active against multiple myeloma (MM), according to preclinical research.
The therapy, known as P-BCMA-101, demonstrated persistent anti-tumor activity in a mouse model of MM.
Treatment with P-BCMA-101 eliminated tumors after relapse and prolonged survival in the mice, when compared to other CAR-T cell therapies.
These results were presented in a poster at the AACR Annual Meeting 2017 (abstract 3759).
The research was conducted by employees of Poseida Therapeutics Inc., the company developing P-BCMA-101, as well as others.
About P-BCMA-101
The researchers explained that P-BCMA-101 employs a B-cell maturation antigen (BCMA)-specific Centyrin™ rather than a single-chain variable fragment (scFv) for antigen detection.
Centyrins™ are fully human and have similar binding affinities as scFvs. However, Centyrins are smaller, more thermostable, and predicted to be less immunogenic.
P-BCMA-101 is engineered using the PiggyBac™ DNA modification system. PiggyBac eliminates the need to use lentivirus or gamma-retrovirus as a gene delivery mechanism, resulting in improved manufacturing and cost savings.
In addition, the increased cargo capacity of PiggyBac allows for the incorporation of a safety switch and a selectable gene. The safety switch can be “flipped” to enable depletion in case adverse events occur. And the selectable gene allows for enrichment of CARTyrin+ cells using a non-genotoxic drug.
Findings
The researchers found that more than 70% of P-BCMA-101 cells possessed a stem cell memory phenotype, creating a significant population of self-renewing, multipotent progenitors capable of reconstituting the entire spectrum of memory and effector T-cell subsets required to prevent cancer relapse. Similar competitor products typically report 0% to 20% stem cell memory phenotype.
In addition, P-BCMA-101 was enriched with more than 95% of T cells successfully modified, which compares favorably to the roughly 30% to 50% commonly expected with clinical manufacture using lentivirus.
P-BCMA-101 did not exhibit effects of CAR-mediated tonic signaling, a common cause of T-cell exhaustion that leads to poor durability. Tonic signaling is caused by oligomerization of unstable binding domains commonly seen with traditional scFv CARs.
The researchers tested P-BCMA-101 in NSG mice bearing luciferase+ MM.1S cells. The mice received a single administration of either 4 x 106 or 12 x 106 P-BCMA-101 cells.
P-BCMA-101 treatment reduced tumor burden to the limit of detection within 7 days. Conversely, all untreated control mice succumbed to MM within 4 weeks.
P-BCMA-101 expanded and persisted in the treated mice, eliminated tumors following relapse, and prolonged survival.
Most treated mice survived 110 days, and none of them died from tumor burden during the study. This compares favorably to lentivirus-based products that have shown roughly 50-day survival in the same model.
Based on these results, Poseida plans to initiate a phase 1 trial of P-BCMA-101 in patients with relapsed or refractory MM.
WASHINGTON, DC—A chimeric antigen receptor (CAR) T-cell therapy is active against multiple myeloma (MM), according to preclinical research.
The therapy, known as P-BCMA-101, demonstrated persistent anti-tumor activity in a mouse model of MM.
Treatment with P-BCMA-101 eliminated tumors after relapse and prolonged survival in the mice, when compared to other CAR-T cell therapies.
These results were presented in a poster at the AACR Annual Meeting 2017 (abstract 3759).
The research was conducted by employees of Poseida Therapeutics Inc., the company developing P-BCMA-101, as well as others.
About P-BCMA-101
The researchers explained that P-BCMA-101 employs a B-cell maturation antigen (BCMA)-specific Centyrin™ rather than a single-chain variable fragment (scFv) for antigen detection.
Centyrins™ are fully human and have similar binding affinities as scFvs. However, Centyrins are smaller, more thermostable, and predicted to be less immunogenic.
P-BCMA-101 is engineered using the PiggyBac™ DNA modification system. PiggyBac eliminates the need to use lentivirus or gamma-retrovirus as a gene delivery mechanism, resulting in improved manufacturing and cost savings.
In addition, the increased cargo capacity of PiggyBac allows for the incorporation of a safety switch and a selectable gene. The safety switch can be “flipped” to enable depletion in case adverse events occur. And the selectable gene allows for enrichment of CARTyrin+ cells using a non-genotoxic drug.
Findings
The researchers found that more than 70% of P-BCMA-101 cells possessed a stem cell memory phenotype, creating a significant population of self-renewing, multipotent progenitors capable of reconstituting the entire spectrum of memory and effector T-cell subsets required to prevent cancer relapse. Similar competitor products typically report 0% to 20% stem cell memory phenotype.
In addition, P-BCMA-101 was enriched with more than 95% of T cells successfully modified, which compares favorably to the roughly 30% to 50% commonly expected with clinical manufacture using lentivirus.
P-BCMA-101 did not exhibit effects of CAR-mediated tonic signaling, a common cause of T-cell exhaustion that leads to poor durability. Tonic signaling is caused by oligomerization of unstable binding domains commonly seen with traditional scFv CARs.
The researchers tested P-BCMA-101 in NSG mice bearing luciferase+ MM.1S cells. The mice received a single administration of either 4 x 106 or 12 x 106 P-BCMA-101 cells.
P-BCMA-101 treatment reduced tumor burden to the limit of detection within 7 days. Conversely, all untreated control mice succumbed to MM within 4 weeks.
P-BCMA-101 expanded and persisted in the treated mice, eliminated tumors following relapse, and prolonged survival.
Most treated mice survived 110 days, and none of them died from tumor burden during the study. This compares favorably to lentivirus-based products that have shown roughly 50-day survival in the same model.
Based on these results, Poseida plans to initiate a phase 1 trial of P-BCMA-101 in patients with relapsed or refractory MM.
Drug granted orphan designation for MM
The US Food and Drug Administration (FDA) has granted orphan drug designation for tasquinimod as a treatment for multiple myeloma (MM).
Tasquinimod is an immunomodulatory, anti-metastatic, and anti-angiogenic compound being developed by Active Biotech AB.
The company says tasquinimod works by inhibiting the function of S100A9, a pro-inflammatory protein that is elevated in MM and other malignancies.
S100A9 is believed to aid cancer development by recruiting and activating immune cells such as myeloid-derived suppressor cells.
Active Biotech AB says that, by targeting the S100A9 pathway, tasquinimod interferes with the accumulation and activation of myeloid-derived suppressor cells in the tumor microenvironment, which decreases immune suppression and angiogenesis.
Tasquinimod also inhibits the hypoxic response in the tumor by binding to HDAC4, according to Active Biotech AB.
The company says tasquinimod has produced “robust results” in animal models of MM, and research presented at the AACR Annual Meeting 2015 supports this statement.
Investigators found that tasquinimod reduced tumor growth and improved survival in mouse models of MM. And these effects were associated with reduced angiogenesis in the bone marrow.
Tasquinimod was previously under development as a treatment for prostate cancer, but research suggested the drug did not have a favorable risk-benefit ratio in this patient population.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.
Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation for tasquinimod as a treatment for multiple myeloma (MM).
Tasquinimod is an immunomodulatory, anti-metastatic, and anti-angiogenic compound being developed by Active Biotech AB.
The company says tasquinimod works by inhibiting the function of S100A9, a pro-inflammatory protein that is elevated in MM and other malignancies.
S100A9 is believed to aid cancer development by recruiting and activating immune cells such as myeloid-derived suppressor cells.
Active Biotech AB says that, by targeting the S100A9 pathway, tasquinimod interferes with the accumulation and activation of myeloid-derived suppressor cells in the tumor microenvironment, which decreases immune suppression and angiogenesis.
Tasquinimod also inhibits the hypoxic response in the tumor by binding to HDAC4, according to Active Biotech AB.
The company says tasquinimod has produced “robust results” in animal models of MM, and research presented at the AACR Annual Meeting 2015 supports this statement.
Investigators found that tasquinimod reduced tumor growth and improved survival in mouse models of MM. And these effects were associated with reduced angiogenesis in the bone marrow.
Tasquinimod was previously under development as a treatment for prostate cancer, but research suggested the drug did not have a favorable risk-benefit ratio in this patient population.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.
Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation for tasquinimod as a treatment for multiple myeloma (MM).
Tasquinimod is an immunomodulatory, anti-metastatic, and anti-angiogenic compound being developed by Active Biotech AB.
The company says tasquinimod works by inhibiting the function of S100A9, a pro-inflammatory protein that is elevated in MM and other malignancies.
S100A9 is believed to aid cancer development by recruiting and activating immune cells such as myeloid-derived suppressor cells.
Active Biotech AB says that, by targeting the S100A9 pathway, tasquinimod interferes with the accumulation and activation of myeloid-derived suppressor cells in the tumor microenvironment, which decreases immune suppression and angiogenesis.
Tasquinimod also inhibits the hypoxic response in the tumor by binding to HDAC4, according to Active Biotech AB.
The company says tasquinimod has produced “robust results” in animal models of MM, and research presented at the AACR Annual Meeting 2015 supports this statement.
Investigators found that tasquinimod reduced tumor growth and improved survival in mouse models of MM. And these effects were associated with reduced angiogenesis in the bone marrow.
Tasquinimod was previously under development as a treatment for prostate cancer, but research suggested the drug did not have a favorable risk-benefit ratio in this patient population.
About orphan designation
The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.
Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.