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Progression-free survival was significantly better when patients with relapsed or refractory mantle-cell lymphoma were treated with oral ibrutinib than with intravenous temsirolimus, based on results from 280 patients in an international, randomized, open-label phase III trial.
Study subjects had undergone one or more previous rituximab-containing chemotherapy regimens to receive intravenous temsirolimus or oral ibrutinib at a daily dose of 560 mg.
Compared with temsirolimus, ibrutinib resulted in a 57% reduction in the risk of disease progression or death at a median follow-up of 20 months. Median progression-free survival – the trial’s primary endpoint – was 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group.
Ibrutinib was also better tolerated, with 68% of patients having grade 3 or higher treatment-emergent adverse events as compared to 87% of patients in the temsirolimus group, despite a median 4-fold longer treatment duration for the ibrutinib group than the temsirolimus group. Additionally, 6% of patients discontinued ibrutinib because of adverse events versus 26% in the temsirolimus group, reported Dr. Martin Dreyling of Klinikum der Universität in Munich, Germany, and his associates.
Based on results of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, ibrutinib was associated with greater and more rapid improvements, and also with less worsening in lymphoma symptoms, as measured by the lymphoma subscale of the FACT-Lym (Lancet. 2016;387:770-78).
Ibrutinib, a first-in-class oral inhibitor of Bruton’s tyrosine kinase, is approved in the United States and the European Union at a dose of 560 mg per day for patients with mantle cell lymphoma who have received at least one previous line of therapy.
The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is approved in the European Union for relapsed or refractory mantle-cell lymphoma, but does not have FDA approval for this indication.
The study, funded by Janssen, is ongoing. Future research, the investigators say, should examine ibrutinib-based combination approaches for patients with relapsed or refractory mantle-cell lymphoma and in front-line therapy.
Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study. Several other authors reported grants from Janssen during the study and financial ties to the company.
The findings from this phase III trial clearly establish ibrutinib as a new standard for treatment of relapsed mantle-cell lymphoma. Within the next 2 years, many expect the agent will find its way into the frontline setting for treatment of mantle cell lymphoma in combination with standard chemotherapy, based on results of another already completed phase III trial (the SHINE trial).
Despite this remarkable progress, however, mantle-cell lymphoma remains incurable. Roughly 30%-40% of people with the disease will not respond to ibrutinib, and even among responders relapse seems inevitable.
Mantle-cell lymphoma has been a model for accelerated development of novel drugs. Ibrutinib was developed with tremendous speed, and the FDA’s approval of the agent in 2013 based on findings from a non-pivotal phase II trial was surprising to everyone other than the participating patients and physicians. Hopefully the resources mobilized to bring ibrutinib so far, so fast, will continue to be available to help us learn how best to use the drug.
Dr. Peter Martin is with the department of medicine at Weill Cornell Medical College in New York. His comments are excerpted from an editorial that accompanied the study in The Lancet. Dr. Martin reported that he is a consultant for Janssen and has received honoraria from the company for speaking.
The findings from this phase III trial clearly establish ibrutinib as a new standard for treatment of relapsed mantle-cell lymphoma. Within the next 2 years, many expect the agent will find its way into the frontline setting for treatment of mantle cell lymphoma in combination with standard chemotherapy, based on results of another already completed phase III trial (the SHINE trial).
Despite this remarkable progress, however, mantle-cell lymphoma remains incurable. Roughly 30%-40% of people with the disease will not respond to ibrutinib, and even among responders relapse seems inevitable.
Mantle-cell lymphoma has been a model for accelerated development of novel drugs. Ibrutinib was developed with tremendous speed, and the FDA’s approval of the agent in 2013 based on findings from a non-pivotal phase II trial was surprising to everyone other than the participating patients and physicians. Hopefully the resources mobilized to bring ibrutinib so far, so fast, will continue to be available to help us learn how best to use the drug.
Dr. Peter Martin is with the department of medicine at Weill Cornell Medical College in New York. His comments are excerpted from an editorial that accompanied the study in The Lancet. Dr. Martin reported that he is a consultant for Janssen and has received honoraria from the company for speaking.
The findings from this phase III trial clearly establish ibrutinib as a new standard for treatment of relapsed mantle-cell lymphoma. Within the next 2 years, many expect the agent will find its way into the frontline setting for treatment of mantle cell lymphoma in combination with standard chemotherapy, based on results of another already completed phase III trial (the SHINE trial).
Despite this remarkable progress, however, mantle-cell lymphoma remains incurable. Roughly 30%-40% of people with the disease will not respond to ibrutinib, and even among responders relapse seems inevitable.
Mantle-cell lymphoma has been a model for accelerated development of novel drugs. Ibrutinib was developed with tremendous speed, and the FDA’s approval of the agent in 2013 based on findings from a non-pivotal phase II trial was surprising to everyone other than the participating patients and physicians. Hopefully the resources mobilized to bring ibrutinib so far, so fast, will continue to be available to help us learn how best to use the drug.
Dr. Peter Martin is with the department of medicine at Weill Cornell Medical College in New York. His comments are excerpted from an editorial that accompanied the study in The Lancet. Dr. Martin reported that he is a consultant for Janssen and has received honoraria from the company for speaking.
Progression-free survival was significantly better when patients with relapsed or refractory mantle-cell lymphoma were treated with oral ibrutinib than with intravenous temsirolimus, based on results from 280 patients in an international, randomized, open-label phase III trial.
Study subjects had undergone one or more previous rituximab-containing chemotherapy regimens to receive intravenous temsirolimus or oral ibrutinib at a daily dose of 560 mg.
Compared with temsirolimus, ibrutinib resulted in a 57% reduction in the risk of disease progression or death at a median follow-up of 20 months. Median progression-free survival – the trial’s primary endpoint – was 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group.
Ibrutinib was also better tolerated, with 68% of patients having grade 3 or higher treatment-emergent adverse events as compared to 87% of patients in the temsirolimus group, despite a median 4-fold longer treatment duration for the ibrutinib group than the temsirolimus group. Additionally, 6% of patients discontinued ibrutinib because of adverse events versus 26% in the temsirolimus group, reported Dr. Martin Dreyling of Klinikum der Universität in Munich, Germany, and his associates.
Based on results of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, ibrutinib was associated with greater and more rapid improvements, and also with less worsening in lymphoma symptoms, as measured by the lymphoma subscale of the FACT-Lym (Lancet. 2016;387:770-78).
Ibrutinib, a first-in-class oral inhibitor of Bruton’s tyrosine kinase, is approved in the United States and the European Union at a dose of 560 mg per day for patients with mantle cell lymphoma who have received at least one previous line of therapy.
The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is approved in the European Union for relapsed or refractory mantle-cell lymphoma, but does not have FDA approval for this indication.
The study, funded by Janssen, is ongoing. Future research, the investigators say, should examine ibrutinib-based combination approaches for patients with relapsed or refractory mantle-cell lymphoma and in front-line therapy.
Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study. Several other authors reported grants from Janssen during the study and financial ties to the company.
Progression-free survival was significantly better when patients with relapsed or refractory mantle-cell lymphoma were treated with oral ibrutinib than with intravenous temsirolimus, based on results from 280 patients in an international, randomized, open-label phase III trial.
Study subjects had undergone one or more previous rituximab-containing chemotherapy regimens to receive intravenous temsirolimus or oral ibrutinib at a daily dose of 560 mg.
Compared with temsirolimus, ibrutinib resulted in a 57% reduction in the risk of disease progression or death at a median follow-up of 20 months. Median progression-free survival – the trial’s primary endpoint – was 14.6 months for the ibrutinib group and 6.2 months for the temsirolimus group.
Ibrutinib was also better tolerated, with 68% of patients having grade 3 or higher treatment-emergent adverse events as compared to 87% of patients in the temsirolimus group, despite a median 4-fold longer treatment duration for the ibrutinib group than the temsirolimus group. Additionally, 6% of patients discontinued ibrutinib because of adverse events versus 26% in the temsirolimus group, reported Dr. Martin Dreyling of Klinikum der Universität in Munich, Germany, and his associates.
Based on results of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire, ibrutinib was associated with greater and more rapid improvements, and also with less worsening in lymphoma symptoms, as measured by the lymphoma subscale of the FACT-Lym (Lancet. 2016;387:770-78).
Ibrutinib, a first-in-class oral inhibitor of Bruton’s tyrosine kinase, is approved in the United States and the European Union at a dose of 560 mg per day for patients with mantle cell lymphoma who have received at least one previous line of therapy.
The mammalian target of rapamycin (mTOR) inhibitor temsirolimus is approved in the European Union for relapsed or refractory mantle-cell lymphoma, but does not have FDA approval for this indication.
The study, funded by Janssen, is ongoing. Future research, the investigators say, should examine ibrutinib-based combination approaches for patients with relapsed or refractory mantle-cell lymphoma and in front-line therapy.
Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study. Several other authors reported grants from Janssen during the study and financial ties to the company.
FROM THE LANCET
Key clinical point: Ibrutinib significantly improved progression-free survival, compared with temsirolimus in patients with relapsed or refractory mantle-cell lymphoma.
Major finding: Median progression-free survival was 14.6 months with ibrutinib and 6.2 months with temsirolimus.
Data source: A randomized open-label phase III trial (ongoing) that randomized 280 patients to each treatment group.
Disclosures: The study was funded by Janssen. Dr. Dreyling reported grants and personal fees from Janssen and Pfizer outside of the study, and other authors reported grants from Janssen during the study and financial ties to the company.
