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CAR T-cell therapy: Moving from cost to value
Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.
“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.
In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
Price tag pressure
During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.
The “list price” for tisagenlecleucel is $475,000, and the potential patient pool is in the hundreds. The price for axicabtagene ciloleucel is $373,000, with a potential market in the thousands. Taking this into account, the global CAR T market is estimated at about $72 million and is projected to expand to nearly $3.5 billion in the next decade, said Dr. Maziarz, who is also chair of the Value and Health Economics Interest Group of the American Society for Blood and Marrow Transplantation.
The market for adoptive cell therapy overall – including transplant, CAR T, natural killer cells, and cell vaccines – is projected by some individuals to be worth $30 billion by 2030, he added, noting, for the sake of comparison, that the total estimated U.S. expenditure for all cancer care in the United States in 2010 was $125 billion.
At the heart of the issue of cost is the matter of value, he said.
“You can talk about price, and you can talk about cost, but … what we want to do with our dollars is buy value – and quality and value are very hard to measure,” he said, noting that he expects public and governmental backlash, as was seen with prior high-cost treatments such as Sovaldi for hepatitis C and Glybera for lipoprotein lipase deficiency.
Value-based payment is a recurrent theme in medicine, and these treatments came under intense scrutiny for their high costs. Sovaldi, for example, costs approximately $90,000 for a treatment course. That sounds like a lot of money, but it cures the disease and can prevent long-term complications, Dr. Maziarz said. Still, it received a lot of negative press, and the backlash was severe.
“People do respond to price,” he said, noting that he predicts the same for CAR T-cell therapies.
The costs of CAR T-cell therapy, particularly when taking into consideration the costs that hospitals will incur given the lymphodepletion that patients experience and the after-care required, will likely exceed those of most stem cell transplants and could easily reach the $1 million-plus estimates, Helen Heslop, MD, professor of medicine and pediatrics and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston, said in an interview.
Aside from the research and development costs, these treatments also cost more to make than any others previously made, according to Carl H. June, MD, the Richard W. Vague Professor In Immunotherapy at the University of Pennsylvania, Philadelphia, and a pioneer in CAR T-cell research.
Dr. June predicted that costs will be forced down over time because of process improvements and competition. “What’s unknown is the time span on how long it will take,” he said in an interview.
Groups like the United Kingdom’s National Institute for Health and Care Excellence (NICE) are already looking at value-based approaches to providing CAR T-cell therapy, Dr. Heslop said.
“I think there will need to be a lot more comparative effectiveness analyses done,” she said. “I know my institution started to look at the cost in a child with ALL once they relapse, and when you look at all the downstream cost, even though [CAR T-cell therapy] sounds very expensive, as a one-time therapy versus much longer treatment, it may actually be value based,” she said.
When it comes to improving access, one of the approaches being studied is the use of universal cell banks as opposed to autologous cells for therapy. This “off-the-shelf” approach, much like the approach used in transfusion medicine, would allow for quicker availability of the cells to a greater number of patients, she said.
Dr. June who, along with Dr. Heslop, cochaired the SITC plenary session on genetically modified cell therapy, agreed, saying that if this approach works with T cells, it would radically change the CAR T landscape in terms of availability and, perhaps – eventually – cost.
Preliminary results from phase I studies (CALM and PALL) of this approach will be presented at the upcoming annual meeting of the American Society of Hematology. The studies are a joint effort by Servier and Cellectis, which joined forces in the development of UCART19, an allogeneic CAR-T product for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia.
Still, value remains an important consideration. If a therapy is expected to extend a pancreatic cancer patient’s life by a month, it’s probably valid to ask if that is cost effective, but if it is potentially curative for a patient with hematologic malignancy, it’s very hard to say they can’t access it, Dr. Heslop said.
Cost-saving proposals
Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.
Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.
In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.
“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.
In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.
In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.
“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.
The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.
Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).
“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.
The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.
Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.
“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”
Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.
Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.
“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.
In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
Price tag pressure
During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.
The “list price” for tisagenlecleucel is $475,000, and the potential patient pool is in the hundreds. The price for axicabtagene ciloleucel is $373,000, with a potential market in the thousands. Taking this into account, the global CAR T market is estimated at about $72 million and is projected to expand to nearly $3.5 billion in the next decade, said Dr. Maziarz, who is also chair of the Value and Health Economics Interest Group of the American Society for Blood and Marrow Transplantation.
The market for adoptive cell therapy overall – including transplant, CAR T, natural killer cells, and cell vaccines – is projected by some individuals to be worth $30 billion by 2030, he added, noting, for the sake of comparison, that the total estimated U.S. expenditure for all cancer care in the United States in 2010 was $125 billion.
At the heart of the issue of cost is the matter of value, he said.
“You can talk about price, and you can talk about cost, but … what we want to do with our dollars is buy value – and quality and value are very hard to measure,” he said, noting that he expects public and governmental backlash, as was seen with prior high-cost treatments such as Sovaldi for hepatitis C and Glybera for lipoprotein lipase deficiency.
Value-based payment is a recurrent theme in medicine, and these treatments came under intense scrutiny for their high costs. Sovaldi, for example, costs approximately $90,000 for a treatment course. That sounds like a lot of money, but it cures the disease and can prevent long-term complications, Dr. Maziarz said. Still, it received a lot of negative press, and the backlash was severe.
“People do respond to price,” he said, noting that he predicts the same for CAR T-cell therapies.
The costs of CAR T-cell therapy, particularly when taking into consideration the costs that hospitals will incur given the lymphodepletion that patients experience and the after-care required, will likely exceed those of most stem cell transplants and could easily reach the $1 million-plus estimates, Helen Heslop, MD, professor of medicine and pediatrics and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston, said in an interview.
Aside from the research and development costs, these treatments also cost more to make than any others previously made, according to Carl H. June, MD, the Richard W. Vague Professor In Immunotherapy at the University of Pennsylvania, Philadelphia, and a pioneer in CAR T-cell research.
Dr. June predicted that costs will be forced down over time because of process improvements and competition. “What’s unknown is the time span on how long it will take,” he said in an interview.
Groups like the United Kingdom’s National Institute for Health and Care Excellence (NICE) are already looking at value-based approaches to providing CAR T-cell therapy, Dr. Heslop said.
“I think there will need to be a lot more comparative effectiveness analyses done,” she said. “I know my institution started to look at the cost in a child with ALL once they relapse, and when you look at all the downstream cost, even though [CAR T-cell therapy] sounds very expensive, as a one-time therapy versus much longer treatment, it may actually be value based,” she said.
When it comes to improving access, one of the approaches being studied is the use of universal cell banks as opposed to autologous cells for therapy. This “off-the-shelf” approach, much like the approach used in transfusion medicine, would allow for quicker availability of the cells to a greater number of patients, she said.
Dr. June who, along with Dr. Heslop, cochaired the SITC plenary session on genetically modified cell therapy, agreed, saying that if this approach works with T cells, it would radically change the CAR T landscape in terms of availability and, perhaps – eventually – cost.
Preliminary results from phase I studies (CALM and PALL) of this approach will be presented at the upcoming annual meeting of the American Society of Hematology. The studies are a joint effort by Servier and Cellectis, which joined forces in the development of UCART19, an allogeneic CAR-T product for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia.
Still, value remains an important consideration. If a therapy is expected to extend a pancreatic cancer patient’s life by a month, it’s probably valid to ask if that is cost effective, but if it is potentially curative for a patient with hematologic malignancy, it’s very hard to say they can’t access it, Dr. Heslop said.
Cost-saving proposals
Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.
Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.
In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.
“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.
In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.
In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.
“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.
The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.
Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).
“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.
The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.
Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.
“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”
Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.
Chimeric antigen receptor (CAR) T-cell therapy has generated a great deal of excitement in recent months with the approval of Novartis’ Kymriah (tisagenlecleucel) for pediatric acute lymphoblastic leukemia and Kite Pharma’s Yescarta (axicabtagene ciloleucel) for relapsed/refractory large B-cell lymphoma in adults, and experts in the field foresee a wave of approvals for additional indications in the coming months.
“CAR T is coming unbelievably fast,” Richard Maziarz, MD, professor of medicine at Oregon Health and Science University, Portland, said in an interview.
In fact, a search of clinicaltrials.gov revealed 120 open CAR T-cell–based therapy trials for cancer and other conditions such as autoimmune diseases, he said.
Price tag pressure
During a plenary session on genetically modified cell therapies at the annual meeting of the Society for Immunotherapy of Cancer, experts and investigators provided a glimpse of what’s in store, including new targets and smarter targeting and combinations that incorporate CAR T-cell therapy to treat solid tumors.
The “list price” for tisagenlecleucel is $475,000, and the potential patient pool is in the hundreds. The price for axicabtagene ciloleucel is $373,000, with a potential market in the thousands. Taking this into account, the global CAR T market is estimated at about $72 million and is projected to expand to nearly $3.5 billion in the next decade, said Dr. Maziarz, who is also chair of the Value and Health Economics Interest Group of the American Society for Blood and Marrow Transplantation.
The market for adoptive cell therapy overall – including transplant, CAR T, natural killer cells, and cell vaccines – is projected by some individuals to be worth $30 billion by 2030, he added, noting, for the sake of comparison, that the total estimated U.S. expenditure for all cancer care in the United States in 2010 was $125 billion.
At the heart of the issue of cost is the matter of value, he said.
“You can talk about price, and you can talk about cost, but … what we want to do with our dollars is buy value – and quality and value are very hard to measure,” he said, noting that he expects public and governmental backlash, as was seen with prior high-cost treatments such as Sovaldi for hepatitis C and Glybera for lipoprotein lipase deficiency.
Value-based payment is a recurrent theme in medicine, and these treatments came under intense scrutiny for their high costs. Sovaldi, for example, costs approximately $90,000 for a treatment course. That sounds like a lot of money, but it cures the disease and can prevent long-term complications, Dr. Maziarz said. Still, it received a lot of negative press, and the backlash was severe.
“People do respond to price,” he said, noting that he predicts the same for CAR T-cell therapies.
The costs of CAR T-cell therapy, particularly when taking into consideration the costs that hospitals will incur given the lymphodepletion that patients experience and the after-care required, will likely exceed those of most stem cell transplants and could easily reach the $1 million-plus estimates, Helen Heslop, MD, professor of medicine and pediatrics and director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Houston, said in an interview.
Aside from the research and development costs, these treatments also cost more to make than any others previously made, according to Carl H. June, MD, the Richard W. Vague Professor In Immunotherapy at the University of Pennsylvania, Philadelphia, and a pioneer in CAR T-cell research.
Dr. June predicted that costs will be forced down over time because of process improvements and competition. “What’s unknown is the time span on how long it will take,” he said in an interview.
Groups like the United Kingdom’s National Institute for Health and Care Excellence (NICE) are already looking at value-based approaches to providing CAR T-cell therapy, Dr. Heslop said.
“I think there will need to be a lot more comparative effectiveness analyses done,” she said. “I know my institution started to look at the cost in a child with ALL once they relapse, and when you look at all the downstream cost, even though [CAR T-cell therapy] sounds very expensive, as a one-time therapy versus much longer treatment, it may actually be value based,” she said.
When it comes to improving access, one of the approaches being studied is the use of universal cell banks as opposed to autologous cells for therapy. This “off-the-shelf” approach, much like the approach used in transfusion medicine, would allow for quicker availability of the cells to a greater number of patients, she said.
Dr. June who, along with Dr. Heslop, cochaired the SITC plenary session on genetically modified cell therapy, agreed, saying that if this approach works with T cells, it would radically change the CAR T landscape in terms of availability and, perhaps – eventually – cost.
Preliminary results from phase I studies (CALM and PALL) of this approach will be presented at the upcoming annual meeting of the American Society of Hematology. The studies are a joint effort by Servier and Cellectis, which joined forces in the development of UCART19, an allogeneic CAR-T product for the treatment of CD19-expressing B-cell acute lymphoblastic leukemia.
Still, value remains an important consideration. If a therapy is expected to extend a pancreatic cancer patient’s life by a month, it’s probably valid to ask if that is cost effective, but if it is potentially curative for a patient with hematologic malignancy, it’s very hard to say they can’t access it, Dr. Heslop said.
Cost-saving proposals
Efforts to address the cost concerns, including proposals for novel payment strategies, are already emerging. One example involves an offer by Novartis to charge for Kymriah only if treated patients go into remission within 1 month. Details of the plan haven’t been released.
Another approach is being considered in Europe and involves a graduated payment system for an investigational regulatory T cell therapy for autoimmune disease, Dr. Maziarz said. For example, if the drug costs $1 million, the government might pay $200,000 the first year and then $100,000 per year if the patient is cured. “If the patient relapses, they can stop their payment, as cure was not achieved,” he explained.
In many discussions about value, the definition is based on quality-adjusted life years (QALY) gained, he said. A recent statement from the American College of Cardiology and the American Heart Association on cost/value methodology, for example, used $50,000 per QALY gained as the cut-off for a good investment. Costs of $50,000 to less than $150,000 per QALY were considered to be of intermediate value, and costs of $150,000 or greater per QALY gained were considered to be of low value.
“A number of payers are using these guidelines to determine what drugs they will put on their portfolio and make available to enrollees,” Dr. Maziarz said.
In anticipation of cost-related issues with CAR T-cell therapy, the Institute for Clinical and Economic Review (ICER) and its California Technology Assessment Forum (CTAP) put out a request for information and input regarding their intent to collaboratively initiate an assessment of CAR T-cell effectiveness and value, he said.
In the meantime, Dr. Maziarz said that most private insurers he’s been in contact with are planning coverage of CAR T-cell therapy but are working out the details of how to do it.
“It’s typically going to involve very, very strict guidelines for the patients who go on therapy – it’s not going to be a liberal use of the product. It will involve strict adherence to the label,” he said.
The real challenge, however, will be in the Medicare and Medicaid programs, because of the current nature of the reimbursement structures and lack of clear procedural codes to define the effort and cost of care associated with the application of these novel cell therapies.
Walid F. Gellad, MD, and Aaron S. Kesselheim, MD, anticipated some of these challenges in light of accelerated approval processes for expensive drugs and proposed in a May 2017 paper that government payers reimburse only the cost of manufacturing and some predetermined mark-up for such drugs until confirmatory trials demonstrate clinical benefit (N Engl J Med. 2017;376[21]:2001-04).
“Both Yescarta and Kymriah are approved with very, very, very limited data – 100 patients, 80 patients. They absolutely look promising. I was part of those studies, so I’m a believer, but the classic approach to determining success in the medical community is a randomized controlled trial,” Dr. Maziarz said.
The proposal by Dr. Gellad and Dr. Kesselheim acknowledged this, and said perhaps full payment isn’t warranted while the drugs remain in development and until they are proven to be a good investment.
Their proposal also calls for an economic impact analysis after 1-2 years on the market for all accelerated-approval pathway drugs that cost over a predetermined amount, timely and optimally designed confirmatory trials following accelerated approval to limit the period of uncertainty about the true clinical effect of the drug, and additional price concessions to public insurance programs for such drugs until the confirmatory trials are completed. Under this proposal, the unpaid portion of drug costs would be held in escrow until the drug’s efficacy is confirmed.
“I think what’s going to happen is that, as prices and costs go up for any therapy, that backlash will occur. These types of proposals to create solutions will come not from individual companies, but from the government,” Dr. Maziarz said. “I’m 100% excited about the work. I’m extremely excited to be part of the explorations. … I just still think we have to at least try to be aware and cognizant of the issues that we’ll be facing.”
Dr. Maziarz has received consulting fees from Novartis, Juno Therapeutics, and Kite Pharma. Dr. Heslop has received consulting fees from Novartis, has conducted research for Cell Medica and holds intellectual property rights/patent from Cell Medica, and has ownership interest in ViraCyte and Marker Therapeutics. Dr. June received royalties from Novartis, has conducted research for Novartis, and has ownership interest in Tmunity Therapeutics.
FDA expands approval of obinutuzumab
The US Food and Drug Administration (FDA) has expanded the approved use of obinutuzumab (Gazyva®).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV) .
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
The FDA granted this new approval of obinutuzumab to Genentech, Inc. The application for obinutuzumab in this indication received priority review.
The latest FDA approval means obinutuzumab is available in the US for the following indications:
- In combination with chlorambucil to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment
- In combination with bendamustine, followed by obinutuzumab alone, to treat FL in adults who did not respond to a rituximab-containing regimen or whose FL returned after such treatment
- In combination with chemotherapy, followed by obinutuzumab alone in responders, to treat stage II bulky, stage III, or stage IV FL in adults who have not had previous FL treatment.
Phase 3 results
The latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were presented at the 2016 ASH Annual Meeting and published in NEJM in October.
The following are updated data from the obinutuzumab prescribing information.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
At a median observation time of 38 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
Safety was evaluated based on all 1385 patients in the study, 86% of whom had previously untreated FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
The most common AEs (incidence ≥ 20%) observed at least 2% more patients in the obinutuzumab arm were infusion-related reactions, neutropenia, upper respiratory tract infection, cough, constipation, and diarrhea.
The most common grade 3 to 5 AEs (incidence ≥ 5%) observed more frequently in the obinutuzumab arm were neutropenia, infusion-related reactions, febrile neutropenia, and thrombocytopenia. 
The US Food and Drug Administration (FDA) has expanded the approved use of obinutuzumab (Gazyva®).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV) .
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
The FDA granted this new approval of obinutuzumab to Genentech, Inc. The application for obinutuzumab in this indication received priority review.
The latest FDA approval means obinutuzumab is available in the US for the following indications:
- In combination with chlorambucil to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment
- In combination with bendamustine, followed by obinutuzumab alone, to treat FL in adults who did not respond to a rituximab-containing regimen or whose FL returned after such treatment
- In combination with chemotherapy, followed by obinutuzumab alone in responders, to treat stage II bulky, stage III, or stage IV FL in adults who have not had previous FL treatment.
Phase 3 results
The latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were presented at the 2016 ASH Annual Meeting and published in NEJM in October.
The following are updated data from the obinutuzumab prescribing information.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
At a median observation time of 38 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
Safety was evaluated based on all 1385 patients in the study, 86% of whom had previously untreated FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
The most common AEs (incidence ≥ 20%) observed at least 2% more patients in the obinutuzumab arm were infusion-related reactions, neutropenia, upper respiratory tract infection, cough, constipation, and diarrhea.
The most common grade 3 to 5 AEs (incidence ≥ 5%) observed more frequently in the obinutuzumab arm were neutropenia, infusion-related reactions, febrile neutropenia, and thrombocytopenia.
The US Food and Drug Administration (FDA) has expanded the approved use of obinutuzumab (Gazyva®).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV) .
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
The FDA granted this new approval of obinutuzumab to Genentech, Inc. The application for obinutuzumab in this indication received priority review.
The latest FDA approval means obinutuzumab is available in the US for the following indications:
- In combination with chlorambucil to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment
- In combination with bendamustine, followed by obinutuzumab alone, to treat FL in adults who did not respond to a rituximab-containing regimen or whose FL returned after such treatment
- In combination with chemotherapy, followed by obinutuzumab alone in responders, to treat stage II bulky, stage III, or stage IV FL in adults who have not had previous FL treatment.
Phase 3 results
The latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were presented at the 2016 ASH Annual Meeting and published in NEJM in October.
The following are updated data from the obinutuzumab prescribing information.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
At a median observation time of 38 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
Safety was evaluated based on all 1385 patients in the study, 86% of whom had previously untreated FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
The most common AEs (incidence ≥ 20%) observed at least 2% more patients in the obinutuzumab arm were infusion-related reactions, neutropenia, upper respiratory tract infection, cough, constipation, and diarrhea.
The most common grade 3 to 5 AEs (incidence ≥ 5%) observed more frequently in the obinutuzumab arm were neutropenia, infusion-related reactions, febrile neutropenia, and thrombocytopenia.
Rituximab key to survival after transplant for mantle cell lymphoma
The study, which outlines the experience across a variety of different treatment patterns at City of Hope National Medical Center, Duarte, Calif., between January 1997 and November 2013, suggests a “large benefit” of adding rituximab, wrote Matthew G. Mei, MD, of the center’s department of hematology and hematopoietic cell transplantation, and his colleagues. Further, maintenance rituximab was associated with improved survival outcomes in patients with positron emission tomography (PET)-negative status at first complete remission.
The benefit of rituximab “stands out, and adds to the increasing body of evidence supporting this practice for all MCL patients after ASCT, regardless of age and frontline induction regimens,” wrote Dr. Mei and his colleagues (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.07.006). This was the case even with improvements in early diagnosis and supportive care, and the incorporation of novel agents such as bortezomib, lenalidomide, and ibrutinib, they wrote, noting significantly better outcomes for patients who underwent ASCT after 2007.
In multivariate analysis, maintenance rituximab therapy after ASCT was the single most important factor associated with improvement in progression-free survival (relative risk [RR], .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Positron emission tomography scans were done prior to ASCT for 133 patients; after ASCT, 105 (79%) were found to be in a PET-negative complete remission. All but one of the patients with PET-negative disease received rituximab before ASCT. For that PET-negative subset, maintenance rituximab was significantly associated with improvements in progression-free survival (RR, .20; 95% CI, .09-.43) and overall survival (RR, .17; 95% CI, .05-.59).
This study represents one of the largest single-center reports to date on MCL patients who have undergone ASCT, according to the authors. “This study also sets the stage for prospective investigation aiming at optimization of maintenance therapy following ASCT.”
Dr. Mei reported no disclosures, and senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium. The study was supported by research funding from the National Cancer Institute.
This study confirms the value of maintenance rituximab for a large cohort of patients with mantle cell lymphoma who have undergone high-dose chemotherapy and autologous stem cell transplantation outside of clinical trials.
The findings also affirm results of a recent phase 3 randomized trial (LyMa) suggesting that in previously untreated MCL patients who have undergone ASCT, rituximab maintenance is superior to observation in improving overall survival and progression-free survival.
However, the most interesting aspect of this study is the positron emission tomography data. Namely, the benefit of rituximab maintenance was apparent in patients regardless of whether they were in a PET-positive or PET-negative first complete remission at ASCT. “This important finding implies that the benefit of rituximab maintenance after ASCT is present for low- and high-risk MCL patients.”
Despite these confirmatory findings, the treatment landscape for MCL has changed significantly in recent years, particularly with the introduction of treatments such as ibrutinib.
In a clinical trial currently underway, the European Mantle Cell Lymphoma Network is evaluating ibrutinib as an upfront treatment for young and fit patients. Specifically, the study compares first-line ASCT and rituximab maintenance, ASCT with ibrutinib maintenance, or a transplant-free approach with ibrutinib and chemotherapy.
Unless and until the data from this study “redefine the value of ASCT in the ibrutinib era, ASCT and rituximab maintenance should be recommended as the standard treatment after ASCT for transplant-eligible patients with MCL.”
Tobias Roider, MD, and Sascha Dietrich, MD, are with the Department of Medicine V, University of Heidelberg, Germany. Their comments are in an editorial (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.09.008). The authors reported no financial disclosures or conflicts of interest.
This study confirms the value of maintenance rituximab for a large cohort of patients with mantle cell lymphoma who have undergone high-dose chemotherapy and autologous stem cell transplantation outside of clinical trials.
The findings also affirm results of a recent phase 3 randomized trial (LyMa) suggesting that in previously untreated MCL patients who have undergone ASCT, rituximab maintenance is superior to observation in improving overall survival and progression-free survival.
However, the most interesting aspect of this study is the positron emission tomography data. Namely, the benefit of rituximab maintenance was apparent in patients regardless of whether they were in a PET-positive or PET-negative first complete remission at ASCT. “This important finding implies that the benefit of rituximab maintenance after ASCT is present for low- and high-risk MCL patients.”
Despite these confirmatory findings, the treatment landscape for MCL has changed significantly in recent years, particularly with the introduction of treatments such as ibrutinib.
In a clinical trial currently underway, the European Mantle Cell Lymphoma Network is evaluating ibrutinib as an upfront treatment for young and fit patients. Specifically, the study compares first-line ASCT and rituximab maintenance, ASCT with ibrutinib maintenance, or a transplant-free approach with ibrutinib and chemotherapy.
Unless and until the data from this study “redefine the value of ASCT in the ibrutinib era, ASCT and rituximab maintenance should be recommended as the standard treatment after ASCT for transplant-eligible patients with MCL.”
Tobias Roider, MD, and Sascha Dietrich, MD, are with the Department of Medicine V, University of Heidelberg, Germany. Their comments are in an editorial (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.09.008). The authors reported no financial disclosures or conflicts of interest.
This study confirms the value of maintenance rituximab for a large cohort of patients with mantle cell lymphoma who have undergone high-dose chemotherapy and autologous stem cell transplantation outside of clinical trials.
The findings also affirm results of a recent phase 3 randomized trial (LyMa) suggesting that in previously untreated MCL patients who have undergone ASCT, rituximab maintenance is superior to observation in improving overall survival and progression-free survival.
However, the most interesting aspect of this study is the positron emission tomography data. Namely, the benefit of rituximab maintenance was apparent in patients regardless of whether they were in a PET-positive or PET-negative first complete remission at ASCT. “This important finding implies that the benefit of rituximab maintenance after ASCT is present for low- and high-risk MCL patients.”
Despite these confirmatory findings, the treatment landscape for MCL has changed significantly in recent years, particularly with the introduction of treatments such as ibrutinib.
In a clinical trial currently underway, the European Mantle Cell Lymphoma Network is evaluating ibrutinib as an upfront treatment for young and fit patients. Specifically, the study compares first-line ASCT and rituximab maintenance, ASCT with ibrutinib maintenance, or a transplant-free approach with ibrutinib and chemotherapy.
Unless and until the data from this study “redefine the value of ASCT in the ibrutinib era, ASCT and rituximab maintenance should be recommended as the standard treatment after ASCT for transplant-eligible patients with MCL.”
Tobias Roider, MD, and Sascha Dietrich, MD, are with the Department of Medicine V, University of Heidelberg, Germany. Their comments are in an editorial (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.09.008). The authors reported no financial disclosures or conflicts of interest.
The study, which outlines the experience across a variety of different treatment patterns at City of Hope National Medical Center, Duarte, Calif., between January 1997 and November 2013, suggests a “large benefit” of adding rituximab, wrote Matthew G. Mei, MD, of the center’s department of hematology and hematopoietic cell transplantation, and his colleagues. Further, maintenance rituximab was associated with improved survival outcomes in patients with positron emission tomography (PET)-negative status at first complete remission.
The benefit of rituximab “stands out, and adds to the increasing body of evidence supporting this practice for all MCL patients after ASCT, regardless of age and frontline induction regimens,” wrote Dr. Mei and his colleagues (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.07.006). This was the case even with improvements in early diagnosis and supportive care, and the incorporation of novel agents such as bortezomib, lenalidomide, and ibrutinib, they wrote, noting significantly better outcomes for patients who underwent ASCT after 2007.
In multivariate analysis, maintenance rituximab therapy after ASCT was the single most important factor associated with improvement in progression-free survival (relative risk [RR], .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Positron emission tomography scans were done prior to ASCT for 133 patients; after ASCT, 105 (79%) were found to be in a PET-negative complete remission. All but one of the patients with PET-negative disease received rituximab before ASCT. For that PET-negative subset, maintenance rituximab was significantly associated with improvements in progression-free survival (RR, .20; 95% CI, .09-.43) and overall survival (RR, .17; 95% CI, .05-.59).
This study represents one of the largest single-center reports to date on MCL patients who have undergone ASCT, according to the authors. “This study also sets the stage for prospective investigation aiming at optimization of maintenance therapy following ASCT.”
Dr. Mei reported no disclosures, and senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium. The study was supported by research funding from the National Cancer Institute.
The study, which outlines the experience across a variety of different treatment patterns at City of Hope National Medical Center, Duarte, Calif., between January 1997 and November 2013, suggests a “large benefit” of adding rituximab, wrote Matthew G. Mei, MD, of the center’s department of hematology and hematopoietic cell transplantation, and his colleagues. Further, maintenance rituximab was associated with improved survival outcomes in patients with positron emission tomography (PET)-negative status at first complete remission.
The benefit of rituximab “stands out, and adds to the increasing body of evidence supporting this practice for all MCL patients after ASCT, regardless of age and frontline induction regimens,” wrote Dr. Mei and his colleagues (Biol Blood Marrow Transplant 2017 November. doi: 10.1016/j.bbmt.2017.07.006). This was the case even with improvements in early diagnosis and supportive care, and the incorporation of novel agents such as bortezomib, lenalidomide, and ibrutinib, they wrote, noting significantly better outcomes for patients who underwent ASCT after 2007.
In multivariate analysis, maintenance rituximab therapy after ASCT was the single most important factor associated with improvement in progression-free survival (relative risk [RR], .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Positron emission tomography scans were done prior to ASCT for 133 patients; after ASCT, 105 (79%) were found to be in a PET-negative complete remission. All but one of the patients with PET-negative disease received rituximab before ASCT. For that PET-negative subset, maintenance rituximab was significantly associated with improvements in progression-free survival (RR, .20; 95% CI, .09-.43) and overall survival (RR, .17; 95% CI, .05-.59).
This study represents one of the largest single-center reports to date on MCL patients who have undergone ASCT, according to the authors. “This study also sets the stage for prospective investigation aiming at optimization of maintenance therapy following ASCT.”
Dr. Mei reported no disclosures, and senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium. The study was supported by research funding from the National Cancer Institute.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Key clinical point: Over time and in many different patterns, rituximab maintenance therapy stood out as the prominent factor influencing survival in patients with mantle cell lymphoma who undergo autologous stem cell transplant.
Major finding: Maintenance rituximab was significantly associated with superior progression-free survival (relative risk, .25; 95% confidence interval, .14-.44) and overall survival (RR, .17; 95% CI, .07-.38).
Data source: Retrospective analysis of data for 191 patients with MCL who underwent ASCT at a medical center in California between January 1997 and November 2013.
Disclosures: The study was supported by research funding from the National Cancer Institute. Senior author Lihua E. Budde, MD, PhD, reported being a member of the Lymphoma Research Foundation MCL consortium.
NCI-MATCH: Nivolumab shows promising activity in noncolorectal cancers
NATIONAL HARBOR, MD. – The immune checkpoint inhibitor nivolumab has promising activity in mismatch repair–deficient noncolorectal cancers, according to preliminary findings from the first sub-arm of the National Cancer Institute’s landmark Molecular Analysis for Therapy Choice (NCI-MATCH) trial.
NCI-MATCH is a 1,173-site precision medicine trial launched in 2015 to study targeted therapies for patients with relapsed/refractory solid tumors, lymphomas, and myelomas. In the first substudy (arm Z1D), the investigators identified 4,900 subjects with samples that could be tested for “actionable molecular abnormalities,” and from among those, they identified 77 with loss of mismatch repair proteins MLH1 or MSH2. Ultimately 47 patients were treated with nivolumab in the substudy.
The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease, said Dr. Azad of Johns Hopkins University, Baltimore.
The patients had a median age of 60 years and were heavily pretreated with a median of three prior therapies. The most common histologies among them were endometrioid endometrial cancer (10 patients), prostate cancer (6 patients), and breast cancer (3 patients).
The safety and tolerability of treatment was as expected for single-agent nivolumab treatment. Toxicity was predominantly low-grade fatigue. Anemia was the most common grade 3 toxicity.
“DNA repair defects due to mismatch repair–deficiency are most commonly caused by silencing of mismatch repair proteins MLH1 or MSH2 and, a little less commonly, MSH6 or PMS2. This can happen through DNA mutation, as well as promoter methylation,” Dr. Azad explained. “In fact, nivolumab has already been tested in patients with mismatch repair–deficient colorectal cancer, both alone and in combination with anti-CTLA-4 ipilimumab ... in addition, pembrolizumab was approved earlier this year for pretreated mismatch repair–deficient cancer.”
“So this formed the nidus for our interest and hypothesis that nivolumab would also have activity in mismatch repair–deficient noncolorectal cancer,” she said.
Study subjects had relapsed/refractory cancers, good end-organ function, and good performance status. They were screened for molecular alterations by centralized testing on fresh biopsy tissue, and mismatch repair deficiency was defined through immunohistochemistry as loss of nuclear expression of MLH1 or MSH2. Patients with mismatch repair–deficient colorectal cancer were excluded.
Those in the nivolumab arm received 3 mg/kg every 2 weeks, and after cycle 4, they could be switched to receive treatment every 4 weeks. Imaging was performed every 2 weeks, and patients were allowed to remain in the study as long as their disease had not progressed. A caveat was that patients with progression within the first 24 weeks, but with no more than four new lesions or 40% increase in tumor index lesions, could remain in the study as long as they were clinically stable.
The overall response rate was compared against a null value of 5%.
“We enrolled 35 patients so that we could have 31 evaluable patients, looking for a signal of 5 or greater responses in that patient group to conclude that the arm was promising and worth further testing,” Dr. Azad said. “This gave us 91.8% power to conclude that an agent was promising if the overall response was truly 25%.”
The study met its primary endpoint, with 8 responses out of 34 evaluable patients, she reported.
“Of note, we had five more patients that had unconfirmed responses. Two of those remained on study at the time of data cutoff, so these response numbers may change as the study matures,” she said.
The disease control rate was 56%, and benefit was seen across tumor histologies, she noted.
“The duration of benefit was compelling for these patients,” she said. “The median time to response was 2.1 cycles, and the 6-month progression-free survival was 49%.”
The median duration of response has not been reached.
Follow-up is ongoing, and 12 patients are enrolled in an expansion cohort; results should be reported within the next year.
“Future work includes interrogating tumor tissue and blood to identify possible predictive markers of response and resistance,” Dr. Azad concluded.
Dr. Azad reported having no disclosures.
NATIONAL HARBOR, MD. – The immune checkpoint inhibitor nivolumab has promising activity in mismatch repair–deficient noncolorectal cancers, according to preliminary findings from the first sub-arm of the National Cancer Institute’s landmark Molecular Analysis for Therapy Choice (NCI-MATCH) trial.
NCI-MATCH is a 1,173-site precision medicine trial launched in 2015 to study targeted therapies for patients with relapsed/refractory solid tumors, lymphomas, and myelomas. In the first substudy (arm Z1D), the investigators identified 4,900 subjects with samples that could be tested for “actionable molecular abnormalities,” and from among those, they identified 77 with loss of mismatch repair proteins MLH1 or MSH2. Ultimately 47 patients were treated with nivolumab in the substudy.
The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease, said Dr. Azad of Johns Hopkins University, Baltimore.
The patients had a median age of 60 years and were heavily pretreated with a median of three prior therapies. The most common histologies among them were endometrioid endometrial cancer (10 patients), prostate cancer (6 patients), and breast cancer (3 patients).
The safety and tolerability of treatment was as expected for single-agent nivolumab treatment. Toxicity was predominantly low-grade fatigue. Anemia was the most common grade 3 toxicity.
“DNA repair defects due to mismatch repair–deficiency are most commonly caused by silencing of mismatch repair proteins MLH1 or MSH2 and, a little less commonly, MSH6 or PMS2. This can happen through DNA mutation, as well as promoter methylation,” Dr. Azad explained. “In fact, nivolumab has already been tested in patients with mismatch repair–deficient colorectal cancer, both alone and in combination with anti-CTLA-4 ipilimumab ... in addition, pembrolizumab was approved earlier this year for pretreated mismatch repair–deficient cancer.”
“So this formed the nidus for our interest and hypothesis that nivolumab would also have activity in mismatch repair–deficient noncolorectal cancer,” she said.
Study subjects had relapsed/refractory cancers, good end-organ function, and good performance status. They were screened for molecular alterations by centralized testing on fresh biopsy tissue, and mismatch repair deficiency was defined through immunohistochemistry as loss of nuclear expression of MLH1 or MSH2. Patients with mismatch repair–deficient colorectal cancer were excluded.
Those in the nivolumab arm received 3 mg/kg every 2 weeks, and after cycle 4, they could be switched to receive treatment every 4 weeks. Imaging was performed every 2 weeks, and patients were allowed to remain in the study as long as their disease had not progressed. A caveat was that patients with progression within the first 24 weeks, but with no more than four new lesions or 40% increase in tumor index lesions, could remain in the study as long as they were clinically stable.
The overall response rate was compared against a null value of 5%.
“We enrolled 35 patients so that we could have 31 evaluable patients, looking for a signal of 5 or greater responses in that patient group to conclude that the arm was promising and worth further testing,” Dr. Azad said. “This gave us 91.8% power to conclude that an agent was promising if the overall response was truly 25%.”
The study met its primary endpoint, with 8 responses out of 34 evaluable patients, she reported.
“Of note, we had five more patients that had unconfirmed responses. Two of those remained on study at the time of data cutoff, so these response numbers may change as the study matures,” she said.
The disease control rate was 56%, and benefit was seen across tumor histologies, she noted.
“The duration of benefit was compelling for these patients,” she said. “The median time to response was 2.1 cycles, and the 6-month progression-free survival was 49%.”
The median duration of response has not been reached.
Follow-up is ongoing, and 12 patients are enrolled in an expansion cohort; results should be reported within the next year.
“Future work includes interrogating tumor tissue and blood to identify possible predictive markers of response and resistance,” Dr. Azad concluded.
Dr. Azad reported having no disclosures.
NATIONAL HARBOR, MD. – The immune checkpoint inhibitor nivolumab has promising activity in mismatch repair–deficient noncolorectal cancers, according to preliminary findings from the first sub-arm of the National Cancer Institute’s landmark Molecular Analysis for Therapy Choice (NCI-MATCH) trial.
NCI-MATCH is a 1,173-site precision medicine trial launched in 2015 to study targeted therapies for patients with relapsed/refractory solid tumors, lymphomas, and myelomas. In the first substudy (arm Z1D), the investigators identified 4,900 subjects with samples that could be tested for “actionable molecular abnormalities,” and from among those, they identified 77 with loss of mismatch repair proteins MLH1 or MSH2. Ultimately 47 patients were treated with nivolumab in the substudy.
The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease, said Dr. Azad of Johns Hopkins University, Baltimore.
The patients had a median age of 60 years and were heavily pretreated with a median of three prior therapies. The most common histologies among them were endometrioid endometrial cancer (10 patients), prostate cancer (6 patients), and breast cancer (3 patients).
The safety and tolerability of treatment was as expected for single-agent nivolumab treatment. Toxicity was predominantly low-grade fatigue. Anemia was the most common grade 3 toxicity.
“DNA repair defects due to mismatch repair–deficiency are most commonly caused by silencing of mismatch repair proteins MLH1 or MSH2 and, a little less commonly, MSH6 or PMS2. This can happen through DNA mutation, as well as promoter methylation,” Dr. Azad explained. “In fact, nivolumab has already been tested in patients with mismatch repair–deficient colorectal cancer, both alone and in combination with anti-CTLA-4 ipilimumab ... in addition, pembrolizumab was approved earlier this year for pretreated mismatch repair–deficient cancer.”
“So this formed the nidus for our interest and hypothesis that nivolumab would also have activity in mismatch repair–deficient noncolorectal cancer,” she said.
Study subjects had relapsed/refractory cancers, good end-organ function, and good performance status. They were screened for molecular alterations by centralized testing on fresh biopsy tissue, and mismatch repair deficiency was defined through immunohistochemistry as loss of nuclear expression of MLH1 or MSH2. Patients with mismatch repair–deficient colorectal cancer were excluded.
Those in the nivolumab arm received 3 mg/kg every 2 weeks, and after cycle 4, they could be switched to receive treatment every 4 weeks. Imaging was performed every 2 weeks, and patients were allowed to remain in the study as long as their disease had not progressed. A caveat was that patients with progression within the first 24 weeks, but with no more than four new lesions or 40% increase in tumor index lesions, could remain in the study as long as they were clinically stable.
The overall response rate was compared against a null value of 5%.
“We enrolled 35 patients so that we could have 31 evaluable patients, looking for a signal of 5 or greater responses in that patient group to conclude that the arm was promising and worth further testing,” Dr. Azad said. “This gave us 91.8% power to conclude that an agent was promising if the overall response was truly 25%.”
The study met its primary endpoint, with 8 responses out of 34 evaluable patients, she reported.
“Of note, we had five more patients that had unconfirmed responses. Two of those remained on study at the time of data cutoff, so these response numbers may change as the study matures,” she said.
The disease control rate was 56%, and benefit was seen across tumor histologies, she noted.
“The duration of benefit was compelling for these patients,” she said. “The median time to response was 2.1 cycles, and the 6-month progression-free survival was 49%.”
The median duration of response has not been reached.
Follow-up is ongoing, and 12 patients are enrolled in an expansion cohort; results should be reported within the next year.
“Future work includes interrogating tumor tissue and blood to identify possible predictive markers of response and resistance,” Dr. Azad concluded.
Dr. Azad reported having no disclosures.
AT SITC 2017
Key clinical point:
Major finding: The confirmed overall response rate was 24%, and an additional 27% of patients had stable disease.
Data source: Arm Z1D (35 patients) of the NCI-MATCH trial.
Disclosures: Dr. Azad reported having no disclosures.
Cancer drug costs increasing despite competition
Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*
Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.
Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).
The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).
For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.
To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.
Results
The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).
The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).
Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.
Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).
Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.
| Drug (indication, approval date, years of follow-up) | Mean monthly cost at launch | Mean annual cost change (SD) | Cumulative cost change | General and health-related inflation-adjusted change, respectively |
| Arsenic trioxide (APL, 2000, 12) | $11,455 | +6% (4) | +95% | +57%, +39% |
| Bendamustine (CLL, NHL, 2008, 8) | $6924 | +5% (5) | +50% | +32%, +21% |
| Bortezomib (MM, MCL, 2003, 12) | $5490 | +4% (3) | +63% | +31%, +16% |
| Brentuximab (lymphoma, 2011, 4) | $19,482 | +8% (0.1) | +35% | +29%, +22% |
| Clofarabine (ALL, 2004, 11) | $56,486 | +3% (3) | +31% | +8%, -4% |
| Liposomal vincristine (ALL, 2012, 3) | $34,602 | +8% (0.5) | +21% | +18%, +14% |
| Nelarabine (ALL, lymphoma, 2005, 10) | $18,513 | +6% (2) | +83% | +55%, +39% |
| Ofatumumab (CLL, 2009, 6) | $4538 | +3% (2) | +17% | +8%, -0.5% |
| Pralatrexate (lymphoma, 2009, 6) | $31,684 | +6% (4) | +43% | +31%, +21% |
| Rituximab (NHL, CLL, 1997, 12) | $4111 | +5% (0.5) | +85% | +49%, +32% |
Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.
The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.
The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.
This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).
*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.
Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*
Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.
Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).
The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).
For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.
To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.
Results
The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).
The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).
Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.
Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).
Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.
| Drug (indication, approval date, years of follow-up) | Mean monthly cost at launch | Mean annual cost change (SD) | Cumulative cost change | General and health-related inflation-adjusted change, respectively |
| Arsenic trioxide (APL, 2000, 12) | $11,455 | +6% (4) | +95% | +57%, +39% |
| Bendamustine (CLL, NHL, 2008, 8) | $6924 | +5% (5) | +50% | +32%, +21% |
| Bortezomib (MM, MCL, 2003, 12) | $5490 | +4% (3) | +63% | +31%, +16% |
| Brentuximab (lymphoma, 2011, 4) | $19,482 | +8% (0.1) | +35% | +29%, +22% |
| Clofarabine (ALL, 2004, 11) | $56,486 | +3% (3) | +31% | +8%, -4% |
| Liposomal vincristine (ALL, 2012, 3) | $34,602 | +8% (0.5) | +21% | +18%, +14% |
| Nelarabine (ALL, lymphoma, 2005, 10) | $18,513 | +6% (2) | +83% | +55%, +39% |
| Ofatumumab (CLL, 2009, 6) | $4538 | +3% (2) | +17% | +8%, -0.5% |
| Pralatrexate (lymphoma, 2009, 6) | $31,684 | +6% (4) | +43% | +31%, +21% |
| Rituximab (NHL, CLL, 1997, 12) | $4111 | +5% (0.5) | +85% | +49%, +32% |
Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.
The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.
The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.
This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).
*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.
Cancer drug costs in the US increase substantially after launch, regardless of competition, according to a study published in the Journal of Clinical Oncology.*
Researchers studied 24 cancer drugs approved over the last 20 years and found a mean cumulative cost increase of about 37%, or 19% when adjusted for inflation.
Among drugs approved to treat hematologic malignancies, the greatest inflation-adjusted price increases were for arsenic trioxide (57%), nelarabine (55%), and rituximab (49%).
The lowest inflation-adjusted price increases were for ofatumumab (8%), clofarabine (8%), and liposomal vincristine (18%).
For this study, Daniel A. Goldstein, MD, of Emory University in Atlanta, Georgia, and his colleagues measured the monthly price trajectories of 24 cancer drugs approved by the US Food and Drug Administration. This included 10 drugs approved to treat hematologic malignancies between 1997 and 2011.
To account for discounts and rebates, the researchers used the average sales prices published by the Centers for Medicare and Medicaid Services and adjusted to general and health-related inflation rates. For each drug, the researchers calculated the cumulative and annual drug cost changes.
Results
The mean follow-up was 8 years. The mean cumulative cost increase for all 24 drugs was +36.5% (95% CI, 24.7% to 48.3%).
The general inflation-adjusted increase was +19.1% (95% CI, 11.0% to 27.2%), and the health-related inflation-adjusted increase was +8.4% (95% CI, 1.4% to 15.4%).
Only 1 of the 24 drugs studied had a price decrease over time. That drug is ziv-aflibercept, which was approved to treat metastatic colorectal cancer in 2012.
Ziv-aflibercept was launched with an annual price exceeding $110,000. After public outcry, the drug’s manufacturer, Sanofi, cut the price in half. By the end of the study’s follow-up period in 2017, the cost of ziv-aflibercept had decreased 13% (inflation-adjusted decrease of 15%, health-related inflation-adjusted decrease of 20%).
Cost changes for the drugs approved to treat hematologic malignancies are listed in the following table.
| Drug (indication, approval date, years of follow-up) | Mean monthly cost at launch | Mean annual cost change (SD) | Cumulative cost change | General and health-related inflation-adjusted change, respectively |
| Arsenic trioxide (APL, 2000, 12) | $11,455 | +6% (4) | +95% | +57%, +39% |
| Bendamustine (CLL, NHL, 2008, 8) | $6924 | +5% (5) | +50% | +32%, +21% |
| Bortezomib (MM, MCL, 2003, 12) | $5490 | +4% (3) | +63% | +31%, +16% |
| Brentuximab (lymphoma, 2011, 4) | $19,482 | +8% (0.1) | +35% | +29%, +22% |
| Clofarabine (ALL, 2004, 11) | $56,486 | +3% (3) | +31% | +8%, -4% |
| Liposomal vincristine (ALL, 2012, 3) | $34,602 | +8% (0.5) | +21% | +18%, +14% |
| Nelarabine (ALL, lymphoma, 2005, 10) | $18,513 | +6% (2) | +83% | +55%, +39% |
| Ofatumumab (CLL, 2009, 6) | $4538 | +3% (2) | +17% | +8%, -0.5% |
| Pralatrexate (lymphoma, 2009, 6) | $31,684 | +6% (4) | +43% | +31%, +21% |
| Rituximab (NHL, CLL, 1997, 12) | $4111 | +5% (0.5) | +85% | +49%, +32% |
Abbreviations: ALL, acute lymphoblastic leukemia; APL, acute promyelocytic leukemia; CLL, chronic lymphocytic leukemia; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; SD, standard deviation.
The researchers noted that there was a steady increase in drug costs over the study period, regardless of whether a drug was granted a new supplemental indication, the drug had a new off-label indication, or a competitor drug was approved.
The only variable that was significantly associated with price change was the amount of time that had elapsed from a drug’s launch.
This association was significant in models in which the researchers used prices adjusted to inflation (P=0.002) and health-related inflation (P=0.023). However, it was not significant when the researchers used the actual drug price (P=0.085).
*Data in the abstract differ from data in the body of the JCO paper. This article includes data from the body of the JCO paper.
Event-free survival at 24 months predicts outcomes in peripheral T-cell lymphomas
Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.
Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.
“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).
PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.
In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.
Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).
Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.
“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.
The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.
Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.
Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.
“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).
PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.
In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.
Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).
Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.
“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.
The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.
Event-free survival at 24 months (EFS24) is predictive of survival in patients with peripheral T-cell lymphomas (PTCLs), according to new findings published in the Journal of Clinical Oncology.
Patients who were event free 2 years after diagnosis had a more favorable outcome, compared with those who relapsed within that time period. Some patients who remained event free for 24 months were potentially cured; conversely, events within 2 years were associated with an early death in almost all of those patients.
“Thus, EFS24 is a dichotomous end point that allows individualized risk prediction in patients with PTCL and can help inform patient counseling, biomarker discovery, clinical trial design, and precision medicine approaches,” wrote Matthew J. Maurer, MS, of the Mayo Clinic, Rochester, MN, and his coauthors (J Clin Oncol. 2017 Oct 26. doi: 10.1200/JCO.2017.73.8195).
PTCL is an uncommon and heterogeneous group of non-Hodgkin lymphomas that carry a very poor prognosis; most systemic cases are treated with anthracycline-based combination chemotherapy. Previous studies have reported that achieving EFS24 is predictive of excellent long-term outcomes, independent of baseline prognostic factors.
In this study Mr. Maurer and his coauthors assessed the association between EFS24 and overall survival in 775 patients with newly systemic PTCL who were diagnosed during 2000-2012 and received treatment with curative intent.
Among the entire cohort, 36% of patients achieved EFS24 while 64% did not, and the median overall survival following progression within that 2-year time period was 4.9 months (95% confidence interval, 3.8-5.9 months). The 5-year overall survival in the group that relapsed was 11%, with a standardized mortality ratio of 46.4 (95% CI, 41.8-51.3).
Conversely, among patients with EFS24, the median overall survival was not reached, and the 5-year overall survival was 78% (95% CI, 73%-84%). In this group, the 5-year risk of subsequent lymphoma relapse was 23%, and survival following a late relapse was generally poor (median of 10.3 months; 95% CI, 5.7-19.1 months). The best outcomes after achieving EFS24 were observed among patients aged 60 years or younger: These patients had a 5-year overall survival of 91%.
“The use of a dichotomous end point that allows individualized risk prediction is particularly important in rare diseases such as PTCL, where limited numbers of patients may make formal surrogate end point analysis difficult,” wrote the authors.
The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Event-free survival at 24 months (EFS24) stratifies outcomes in peripheral T-cell lymphomas.
Major finding: Five-year overall survival for those who achieved EFS24 was 78% vs. 11% for those who did not.
Data source: Multinational cohort study that included 775 patients with newly diagnosed PTCL who were evaluated for EFS24 as a predictive endpoint.
Disclosures: The study was supported by grants from the National Cancer Institute, the Terry Fox Research Institute, and the BC Cancer Foundation. Dr. Maurer reported research funding from Kite Pharma and Celgene, and several of the coauthors reported relationships with industry.
Nivolumab linked to CNS disorder in case report
Autoimmune encephalitis may be a potentially severe complication of immune checkpoint inhibitor therapy, a case report suggests.
The recently published report describes a 53-year-old man with B-cell non-Hodgkin lymphoma who presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with the immune checkpoint inhibitor nivolumab.
Neuropathologic examination of a biopsied brain lesion found on cranial MRI showed a T cell–dominated inflammatory process thought to be autoimmune in origin, according to Herwig Strik, MD, of the department of neurology at Philipps University of Marburg (Germany), and his colleagues (Eur J Cancer. 2017 Oct 16. doi: 10.1016/j.ejca.2017.09.026).
After the patient stopped taking nivolumab and the inflammatory process was treated, his “clinical neurological and radiological status remained stable but disabling with fluctuating dysarthria and ataxia,” Dr. Strik and his colleagues wrote.
“Since these novel anticancer agents are increasingly used, this severe complication should be recognized soon and treatment should be terminated to avoid chronification,” they said in the report.
Nivolumab and other checkpoint inhibitors are known to have autoimmune side effects in some cases that can affect the pulmonary, gastrointestinal, and endocrine systems, the authors said.
Several previous case reports have detailed encephalitis occurring in cancer patients receiving nivolumab, the combination of nivolumab plus the immune checkpoint inhibitor ipilimumab, or ipilimumab alone. The authors said they believe that this case report is the first to describe multifocal CNS inflammation following nivolumab treatment for systemic lymphoma.
The patient was diagnosed with B-cell non-Hodgkin lymphoma in 2005, according to the case report. He was first treated in 2009 with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), followed by stem cell apheresis, radioimmunotherapy, and rituximab; he then received R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) in August 2014, followed by autologous stem cell transplantation in October of that year. The patient started nivolumab maintenance therapy in February 2015 but started experiencing neurological symptoms that eventually led to ending nivolumab treatment in September 2015.
The patient’s lymphoma relapsed in June 2016. “The disabling neurological symptoms and his personal situation, however, worsened the patient’s depressive symptoms so severely that he went abroad to commit assisted suicide,” wrote Dr. Strik and his colleagues.
The authors proposed the term “immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD)” to describe the inflammatory condition described in the case report.
They declared no conflicts of interest related to the case report and did not receive grant support for conducting the research described in it.
Autoimmune encephalitis may be a potentially severe complication of immune checkpoint inhibitor therapy, a case report suggests.
The recently published report describes a 53-year-old man with B-cell non-Hodgkin lymphoma who presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with the immune checkpoint inhibitor nivolumab.
Neuropathologic examination of a biopsied brain lesion found on cranial MRI showed a T cell–dominated inflammatory process thought to be autoimmune in origin, according to Herwig Strik, MD, of the department of neurology at Philipps University of Marburg (Germany), and his colleagues (Eur J Cancer. 2017 Oct 16. doi: 10.1016/j.ejca.2017.09.026).
After the patient stopped taking nivolumab and the inflammatory process was treated, his “clinical neurological and radiological status remained stable but disabling with fluctuating dysarthria and ataxia,” Dr. Strik and his colleagues wrote.
“Since these novel anticancer agents are increasingly used, this severe complication should be recognized soon and treatment should be terminated to avoid chronification,” they said in the report.
Nivolumab and other checkpoint inhibitors are known to have autoimmune side effects in some cases that can affect the pulmonary, gastrointestinal, and endocrine systems, the authors said.
Several previous case reports have detailed encephalitis occurring in cancer patients receiving nivolumab, the combination of nivolumab plus the immune checkpoint inhibitor ipilimumab, or ipilimumab alone. The authors said they believe that this case report is the first to describe multifocal CNS inflammation following nivolumab treatment for systemic lymphoma.
The patient was diagnosed with B-cell non-Hodgkin lymphoma in 2005, according to the case report. He was first treated in 2009 with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), followed by stem cell apheresis, radioimmunotherapy, and rituximab; he then received R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) in August 2014, followed by autologous stem cell transplantation in October of that year. The patient started nivolumab maintenance therapy in February 2015 but started experiencing neurological symptoms that eventually led to ending nivolumab treatment in September 2015.
The patient’s lymphoma relapsed in June 2016. “The disabling neurological symptoms and his personal situation, however, worsened the patient’s depressive symptoms so severely that he went abroad to commit assisted suicide,” wrote Dr. Strik and his colleagues.
The authors proposed the term “immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD)” to describe the inflammatory condition described in the case report.
They declared no conflicts of interest related to the case report and did not receive grant support for conducting the research described in it.
Autoimmune encephalitis may be a potentially severe complication of immune checkpoint inhibitor therapy, a case report suggests.
The recently published report describes a 53-year-old man with B-cell non-Hodgkin lymphoma who presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with the immune checkpoint inhibitor nivolumab.
Neuropathologic examination of a biopsied brain lesion found on cranial MRI showed a T cell–dominated inflammatory process thought to be autoimmune in origin, according to Herwig Strik, MD, of the department of neurology at Philipps University of Marburg (Germany), and his colleagues (Eur J Cancer. 2017 Oct 16. doi: 10.1016/j.ejca.2017.09.026).
After the patient stopped taking nivolumab and the inflammatory process was treated, his “clinical neurological and radiological status remained stable but disabling with fluctuating dysarthria and ataxia,” Dr. Strik and his colleagues wrote.
“Since these novel anticancer agents are increasingly used, this severe complication should be recognized soon and treatment should be terminated to avoid chronification,” they said in the report.
Nivolumab and other checkpoint inhibitors are known to have autoimmune side effects in some cases that can affect the pulmonary, gastrointestinal, and endocrine systems, the authors said.
Several previous case reports have detailed encephalitis occurring in cancer patients receiving nivolumab, the combination of nivolumab plus the immune checkpoint inhibitor ipilimumab, or ipilimumab alone. The authors said they believe that this case report is the first to describe multifocal CNS inflammation following nivolumab treatment for systemic lymphoma.
The patient was diagnosed with B-cell non-Hodgkin lymphoma in 2005, according to the case report. He was first treated in 2009 with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), followed by stem cell apheresis, radioimmunotherapy, and rituximab; he then received R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) in August 2014, followed by autologous stem cell transplantation in October of that year. The patient started nivolumab maintenance therapy in February 2015 but started experiencing neurological symptoms that eventually led to ending nivolumab treatment in September 2015.
The patient’s lymphoma relapsed in June 2016. “The disabling neurological symptoms and his personal situation, however, worsened the patient’s depressive symptoms so severely that he went abroad to commit assisted suicide,” wrote Dr. Strik and his colleagues.
The authors proposed the term “immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD)” to describe the inflammatory condition described in the case report.
They declared no conflicts of interest related to the case report and did not receive grant support for conducting the research described in it.
FROM THE EUROPEAN JOURNAL OF CANCER
Key clinical point: Autoimmune encephalitis may be a potential complication of checkpoint inhibitor therapy.
Major finding: A patient with B-cell non-Hodgkin lymphoma presented with double vision, ataxia, impaired speech, and mild cognitive dysfunction following treatment with nivolumab. Examination of a brain lesion showed a T cell–dominated inflammatory process thought to be autoimmune in origin.
Data source: A case report of a 53-year-old man with B-cell non-Hodgkin lymphoma (B-NHL) who received nivolumab maintenance treatment.
Disclosures: The authors declared no conflicts of interest and did not receive grant support for the research.
FDA approves drug to treat rel/ref MCL
The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).
The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.
This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.
The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.
The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.
Phase 2 trial
The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.
According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.
The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).
Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.
According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.
This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.
The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).
The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.
This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.
The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.
The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.
Phase 2 trial
The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.
According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.
The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).
Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.
According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.
This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.
The US Food and Drug Administration (FDA) has granted accelerated approval to the BTK inhibitor acalabrutinib (Calquence, formerly ACP-196).
The drug is now approved to treat adults with mantle cell lymphoma (MCL) who have received at least 1 prior therapy.
The FDA’s accelerated approval pathway is used for drugs intended to treat serious conditions where there is unmet medical need and when said drugs have demonstrated effects that suggest they will provide a clinical benefit to patients.
This means further study is required to verify and describe the anticipated clinical benefits of acalabrutinib, which was approved based on the overall response rate observed in a phase 2 trial.
The company developing acalabrutinib, AstraZeneca Pharmaceuticals LP, is currently conducting the necessary additional research.
The FDA previously granted AstraZeneca priority review, breakthrough therapy, and orphan drug designations for acalabrutinib as a treatment for MCL.
Phase 2 trial
The FDA approved acalabrutinib based on results of the phase 2 ACE-LY-004 trial. This single-arm trial enrolled 124 adults with relapsed or refractory MCL.
According to AstraZeneca, acalabrutinib produced an overall response rate of 80%, with 40% of patients achieving a complete response and 40% experiencing a partial response.
The most common adverse events (AEs) of any grade (occurring in at least 20% of patients) were anemia (46%), thrombocytopenia (44%), headache (39%), neutropenia (36%), diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%).
Dosage reductions due to AEs occurred in 1.6% of patients. Discontinuations due to AEs occurred in 6.5% of patients. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.
According to AstraZeneca, full results from ACE-LY-004 have been submitted for presentation at an upcoming medical meeting.
This will be the first MCL trial data to be presented from the acalabrutinib development program, which includes both monotherapy and combination therapies in hematologic and solid tumor malignancies.
CCSs more likely to stay at jobs to keep health insurance
Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.
CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.
Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.
The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.
The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).
Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).
Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.
Results
CCSs were more likely than siblings to report:
- Job lock—23.2% and 16.9%, respectively (P=0.16)
- Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
- Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).
In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).
In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).
The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.
“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”
“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”
Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.
Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.
CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.
Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.
The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.
The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).
Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).
Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.
Results
CCSs were more likely than siblings to report:
- Job lock—23.2% and 16.9%, respectively (P=0.16)
- Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
- Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).
In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).
In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).
The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.
“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”
“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”
Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.
Survey results suggest childhood cancer survivors (CCSs) in the US are more likely than individuals without a history of cancer to experience “job lock,” or staying at a job to keep work-related health insurance.
CCSs are also more likely than individuals without a history of cancer to report problems paying medical bills and being denied health insurance.
Anne Kirchhoff, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City, and her colleagues reported these findings in JAMA Oncology.
The researchers analyzed 394 CCSs from pediatric oncology institutions across the US, along with 128 of their siblings who had no history of cancer. All study participants worked 35 hours or more per week.
The most common cancer diagnosis among CCSs was leukemia (35.4%), followed by Hodgkin lymphoma (14.9%). Most patients had undergone chemotherapy (77.2%), radiotherapy (63.9%), and surgery (81.1%).
Overall, sociodemographic and clinical characteristics were similar between CCSs and siblings. However, CCSs were more likely than siblings to have severe, disabling, or life-threatening chronic conditions—33.9% and 17.7%, respectively (P<0.001).
Most CCSs (88.0%) and siblings (88.5%) had employer-sponsored health insurance. Three percent of siblings and 5.3% of CCSs had individual insurance; 1.9% and 2.3%, respectively, had public insurance; and 6.7% and 4.4%, respectively, were uninsured.
Results
CCSs were more likely than siblings to report:
- Job lock—23.2% and 16.9%, respectively (P=0.16)
- Problems paying medical bills—20.1% and 12.9%, respectively (P=0.09)
- Denial of health insurance—13.4% and 1.8%, respectively (P<0.001).
In a multivariable analysis, insurance denial remained significantly more common among CCSs than siblings (relative risk [RR]=7.38).
In another multivariable analysis, 38% of CCSs with a previous insurance denial reported job lock, compared with 20% of those who never experienced insurance denial (RR=1.60). And 44% of CCSs who reported problems paying their medical bills also reported job lock, compared to 16% of those who had no problems paying medical bills (RR=2.43).
The researchers also found that female CCSs (RR=1.70) and CCSs with severe, disabling, or life-threatening chronic conditions (RR=1.72) were more likely to report job lock.
“This information gives us a feel for high-risk groups of survivors who may need more information about insurance,” Dr Kirchhoff said. “Many people experience a gap in education and literacy around insurance, and it’s important for people to understand their options—even those who are employed and consistently had access to insurance through work. We want to know what their concerns are so we can help patients and survivors. Getting healthcare should not be a worry for cancer survivors.”
“Survivors have been through a lot when they were younger and understand the importance of making sure they can get healthcare when they need it. I think a lot of them also saw what their parents and families went through in terms of the financial stress and burden of dealing with a health crisis. So they’re just primed to understand the importance of health insurance.”
Dr Kirchhoff noted that this study was conducted as the Affordable Care Act was rolling out. Therefore, she would like to do a follow-up study to see if the insurance exchanges and Medicaid expansion lessened job-related insurance worries.
Drug receives breakthrough designation for DLBCL
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.
The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).
In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.
Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.
The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.
The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.
“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.
“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”
The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.
*Data in the abstract differ from the data presented at the meeting.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.
The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).
In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.
Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.
The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.
The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.
“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.
“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”
The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.
*Data in the abstract differ from the data presented at the meeting.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to MOR208, an Fc-enhanced monoclonal antibody directed against CD19.
The designation is for MOR208 to be used in combination with lenalidomide to treat adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for high-dose chemotherapy and autologous stem cell transplant.
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The breakthrough designation for MOR208 is based on preliminary data from the ongoing phase 2 L-MIND study (NCT02399085).
In this trial, researchers are evaluating MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are ineligible for high-dose chemotherapy and autologous stem cell transplant.
Preliminary data from this trial were presented at ASCO 2017.* Of the 44 patients enrolled at the data cut-off, 34 were evaluable for efficacy.
The objective response rate was 56% (19/34), and the complete response rate was 32% (11/34). Sixteen of the 19 responders were still on study at the data cut-off point.
The most frequent adverse events of grade 3 or higher were neutropenia (32%), thrombocytopenia (9%), and leukopenia (9%). As of the data cut-off, 27% of patients required a reduction of the lenalidomide dose due to side effects.
“We expect to report further data from our ongoing phase 2 L-MIND trial with MOR208 plus lenalidomide at this year’s American Society of Hematology conference in December,” said Malte Peters, chief development officer of MorphoSys AG, the company developing MOR208.
“In addition, we are currently evaluating MOR208 in combination with bendamustine in our phase 3 B-MIND trial.”
The B-MIND study is designed to compare MOR208 plus bendamustine to rituximab plus bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy and autologous stem cell transplant.
*Data in the abstract differ from the data presented at the meeting.