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Newer blood cancer drugs may not improve OS, QOL
A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.
Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.
None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.
Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.
These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.
All cancer drugs
Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.
There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.
For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.
There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.
The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).
Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.
All cancer trials
The 68 approvals of cancer drugs were supported by 72 clinical trials.
Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.
Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.
Hematology trials and drugs
Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.
The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.
The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).
OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.
There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:
- Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
- Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
- Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).
There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:
- Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
- Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab
For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:
- Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
- Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
- Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
- Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
- Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
- Dasatinib for first-line treatment of chronic phase, Ph+ CML
- Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
- Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
- Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
- Rituximab as maintenance after induction for patients with follicular lymphoma
- Rituximab plus chemotherapy for relapsed or refractory CLL
- Temsirolimus for relapsed or refractory mantle cell lymphoma.
A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.
Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.
None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.
Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.
These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.
All cancer drugs
Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.
There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.
For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.
There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.
The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).
Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.
All cancer trials
The 68 approvals of cancer drugs were supported by 72 clinical trials.
Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.
Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.
Hematology trials and drugs
Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.
The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.
The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).
OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.
There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:
- Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
- Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
- Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).
There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:
- Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
- Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab
For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:
- Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
- Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
- Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
- Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
- Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
- Dasatinib for first-line treatment of chronic phase, Ph+ CML
- Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
- Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
- Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
- Rituximab as maintenance after induction for patients with follicular lymphoma
- Rituximab plus chemotherapy for relapsed or refractory CLL
- Temsirolimus for relapsed or refractory mantle cell lymphoma.
A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.
Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.
None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.
Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.
These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.
All cancer drugs
Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.
There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.
For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.
There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.
The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).
Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.
All cancer trials
The 68 approvals of cancer drugs were supported by 72 clinical trials.
Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.
Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.
Hematology trials and drugs
Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.
The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.
The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).
OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.
There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:
- Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
- Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
- Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).
There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:
- Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
- Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab
For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:
- Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
- Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
- Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
- Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
- Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
- Dasatinib for first-line treatment of chronic phase, Ph+ CML
- Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
- Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
- Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
- Rituximab as maintenance after induction for patients with follicular lymphoma
- Rituximab plus chemotherapy for relapsed or refractory CLL
- Temsirolimus for relapsed or refractory mantle cell lymphoma.
EC expands approval of obinutuzumab in FL
The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.
This is the third EC approval for obinutuzumab.
The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.
The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.
The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with 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.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.
This is the third EC approval for obinutuzumab.
The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.
The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.
The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with 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.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.
This is the third EC approval for obinutuzumab.
The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.
In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.
The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.
The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with 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.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
FDA grants accelerated approval to copanlisib for relapsed follicular lymphoma
The Food and Drug Administration has granted accelerated approval to copanlisib (Aliqopa) for the treatment of adults with relapsed follicular lymphoma who have received at least two prior treatments.
Approval of the kinase inhibitor was based on an overall response rate of 59% in a single-arm trial of 104 patients with follicular B-cell non-Hodgkin lymphoma who had relapsed disease following at least two prior treatments. These patients had a complete or partial response for a median 12.2 months.
“For patients with relapsed follicular lymphoma, the cancer often comes back even after multiple treatments,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the press release. “Options are limited for these patients and today’s approval provides an additional choice for treatment, filling an unmet need for them,” he said.
The Food and Drug Administration has granted accelerated approval to copanlisib (Aliqopa) for the treatment of adults with relapsed follicular lymphoma who have received at least two prior treatments.
Approval of the kinase inhibitor was based on an overall response rate of 59% in a single-arm trial of 104 patients with follicular B-cell non-Hodgkin lymphoma who had relapsed disease following at least two prior treatments. These patients had a complete or partial response for a median 12.2 months.
“For patients with relapsed follicular lymphoma, the cancer often comes back even after multiple treatments,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the press release. “Options are limited for these patients and today’s approval provides an additional choice for treatment, filling an unmet need for them,” he said.
The Food and Drug Administration has granted accelerated approval to copanlisib (Aliqopa) for the treatment of adults with relapsed follicular lymphoma who have received at least two prior treatments.
Approval of the kinase inhibitor was based on an overall response rate of 59% in a single-arm trial of 104 patients with follicular B-cell non-Hodgkin lymphoma who had relapsed disease following at least two prior treatments. These patients had a complete or partial response for a median 12.2 months.
“For patients with relapsed follicular lymphoma, the cancer often comes back even after multiple treatments,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the press release. “Options are limited for these patients and today’s approval provides an additional choice for treatment, filling an unmet need for them,” he said.
Trials of atezolizumab placed on partial hold
Roche has announced a partial clinical hold on 2 trials of the anti-PD-L1 antibody atezolizumab (Tecentriq).
One is a phase 1b/2 study (NCT02631577) in which researchers are evaluating atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma.
The other is a phase 1b study (NCT02431208) of atezolizumab alone or in combination with an immunomodulatory drug and/or daratumumab in patients with multiple myeloma (MM).
The partial clinical hold on these trials means patients who are currently enrolled and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled.
The decision to place these trials on hold is related to risks identified in 2 trials of the anti-PD-1 agent pembrolizumab. Results from these trials showed that combining pembrolizumab with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) increases the risk of death in patients with MM.
The results led to clinical holds on these trials (and a third trial of pembrolizumab) as well as an investigation by the US Food and Drug Administration (FDA).
The FDA has stressed its belief that the benefits of taking pembrolizumab and other PD-1/PD-L1 inhibitors for their approved uses continue to outweigh the risks.
However, the agency also thinks there may be an unfavorable risk-benefit ratio for patients receiving PD-1/PD-L1 treatment alone or in other combinations in unapproved indications.
Therefore, the FDA is investigating trials of PD-1/PD-L1 inhibitors being studied in combination with immunomodulatory agents or other classes of drugs in patients with hematologic malignancies.
In the course of this investigation, the FDA has placed holds on trials of nivolumab and durvalumab as well as atezolizumab.
According to Roche, there is no evidence of an increased risk of death or serious events with the use of atezolizumab in combination with immunomodulatory agents.
Roche has announced a partial clinical hold on 2 trials of the anti-PD-L1 antibody atezolizumab (Tecentriq).
One is a phase 1b/2 study (NCT02631577) in which researchers are evaluating atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma.
The other is a phase 1b study (NCT02431208) of atezolizumab alone or in combination with an immunomodulatory drug and/or daratumumab in patients with multiple myeloma (MM).
The partial clinical hold on these trials means patients who are currently enrolled and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled.
The decision to place these trials on hold is related to risks identified in 2 trials of the anti-PD-1 agent pembrolizumab. Results from these trials showed that combining pembrolizumab with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) increases the risk of death in patients with MM.
The results led to clinical holds on these trials (and a third trial of pembrolizumab) as well as an investigation by the US Food and Drug Administration (FDA).
The FDA has stressed its belief that the benefits of taking pembrolizumab and other PD-1/PD-L1 inhibitors for their approved uses continue to outweigh the risks.
However, the agency also thinks there may be an unfavorable risk-benefit ratio for patients receiving PD-1/PD-L1 treatment alone or in other combinations in unapproved indications.
Therefore, the FDA is investigating trials of PD-1/PD-L1 inhibitors being studied in combination with immunomodulatory agents or other classes of drugs in patients with hematologic malignancies.
In the course of this investigation, the FDA has placed holds on trials of nivolumab and durvalumab as well as atezolizumab.
According to Roche, there is no evidence of an increased risk of death or serious events with the use of atezolizumab in combination with immunomodulatory agents.
Roche has announced a partial clinical hold on 2 trials of the anti-PD-L1 antibody atezolizumab (Tecentriq).
One is a phase 1b/2 study (NCT02631577) in which researchers are evaluating atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma.
The other is a phase 1b study (NCT02431208) of atezolizumab alone or in combination with an immunomodulatory drug and/or daratumumab in patients with multiple myeloma (MM).
The partial clinical hold on these trials means patients who are currently enrolled and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled.
The decision to place these trials on hold is related to risks identified in 2 trials of the anti-PD-1 agent pembrolizumab. Results from these trials showed that combining pembrolizumab with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) increases the risk of death in patients with MM.
The results led to clinical holds on these trials (and a third trial of pembrolizumab) as well as an investigation by the US Food and Drug Administration (FDA).
The FDA has stressed its belief that the benefits of taking pembrolizumab and other PD-1/PD-L1 inhibitors for their approved uses continue to outweigh the risks.
However, the agency also thinks there may be an unfavorable risk-benefit ratio for patients receiving PD-1/PD-L1 treatment alone or in other combinations in unapproved indications.
Therefore, the FDA is investigating trials of PD-1/PD-L1 inhibitors being studied in combination with immunomodulatory agents or other classes of drugs in patients with hematologic malignancies.
In the course of this investigation, the FDA has placed holds on trials of nivolumab and durvalumab as well as atezolizumab.
According to Roche, there is no evidence of an increased risk of death or serious events with the use of atezolizumab in combination with immunomodulatory agents.
FDA approves drug to treat relapsed FL
The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.
The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.
Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.
The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.
Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.
According to Bayer, copanlisib is now available. The prescribing information is available for download here.
In addition, Bayer has created the Aliqopa™ Resource Connections (ARCTM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.
The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.
Phase 2 results
The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.
The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.
The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.
The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).
The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).
There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.
The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.
The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.
Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.
The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.
Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.
According to Bayer, copanlisib is now available. The prescribing information is available for download here.
In addition, Bayer has created the Aliqopa™ Resource Connections (ARCTM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.
The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.
Phase 2 results
The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.
The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.
The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.
The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).
The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).
There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.
The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.
The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.
Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.
The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.
Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.
Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.
According to Bayer, copanlisib is now available. The prescribing information is available for download here.
In addition, Bayer has created the Aliqopa™ Resource Connections (ARCTM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.
The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.
Phase 2 results
The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.
The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.
The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.
The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).
The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).
There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.
Immune status linked to outcomes of CAR T-cell therapy
MAINZ/FRANKFURT, GERMANY—Outcomes of treatment with a third-generation chimeric antigen receptor (CAR) T-cell therapy are associated with a patient’s immune status, according to a phase 1/2a trial.
The CD19-specific CAR T-cell therapy produced a complete response (CR) in 6 of 15 patients with relapsed/refractory CD19-positive leukemia or lymphoma.
Though all responders eventually relapsed, 4 patients—including 2 with stable disease (SD) after treatment—responded to subsequent therapy and are still alive, 1 of them beyond 36 months.
An analysis of blood samples taken throughout the study revealed that a patient’s immune status was associated with treatment failure and overall survival.
Tanja Lövgren, PhD, of Uppsala University in Sweden, and her colleagues presented these findings at the Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (abstract B156).
“CD19-specific CAR T-cell therapy has yielded remarkable response rates for patients who have B-cell acute lymphoblastic leukemia,” Dr Lövgren said. “However, many patients relapse.”
“In addition, response rates are more variable for patients who have other CD19-positive B-cell malignancies, and many patients experience serious adverse events. We set out to investigate the safety and effectiveness of a third-generation CD19-specific CAR T-cell therapy and to identify potential biomarkers of treatment outcome.”
Dr Lövgren and her colleagues studied 15 patients (ages 24-72) who had relapsed or refractory CD19-positive B-cell malignancies:
- Six patients with diffuse large B-cell lymphoma (DLBCL), including 3 cases that were transformed from follicular lymphoma (FL)
- Four patients with pre-B acute lymphoblastic leukemia (ALL)
- Two patients with mantle cell lymphoma (MCL)
- Two patients with chronic lymphocytic leukemia (CLL)
- One patient with FL transformed from Burkitt lymphoma.
Eleven patients received preconditioning with cyclophosphamide (500 mg/m2) and fludarabine (3 doses at 25 mg/m2).
All patients received CAR T cells at 1 x 108, 2 x 107, or 2 x 108 cells/m2. These were autologous, CD19-targeting CAR T cells with 3 intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB.
The researchers assessed tumor responses via bone marrow/blood analysis and/or radiology, depending on the type of malignancy. The team also collected blood samples before CAR T-cell infusion and at multiple times after infusion.
Efficacy and safety
Six patients achieved a CR to treatment—3 with DLBCL (1 transformed), 2 with ALL, and 1 with CLL. Two patients had SD—1 with MCL and 1 with CLL. The remaining patients progressed.
All patients with a CR eventually relapsed. The median duration of CR was 5 months (range, 3-24 months).
Four patients—2 complete responders and 2 with SD—responded well to subsequent therapy and are still alive with 27 to 36 months of follow-up. This includes 1 patient with DLBCL, 1 with MCL, and 2 with CLL.
Four patients had serious adverse events. Three had cytokine-release syndrome, and 2 had neurological toxicity.
All cases of cytokine-release syndrome resolved after treatment with corticosteroids/anti-IL6R therapy. The neurological toxicity resolved spontaneously.
Immune status
An analysis of the blood samples taken throughout the study showed that high levels of monocytic myeloid-derived suppressor cells (MDSCs) prior to treatment was associated with decreased overall survival. In addition, increased levels of MDSCs after treatment preceded treatment failure.
Furthermore, high plasma levels of immunosuppressive factors—such as PD-L1 and PD-L2—after treatment were associated with decreased overall survival.
High plasma levels of biomarkers of an immunostimulatory environment—including IL-12, DC-LAMP, TRAIL, and FasL—before the administration of CAR T-cell therapy was associated with increased overall survival.
“[A]n immunostimulatory environment was associated with improved overall survival, while immunosuppressive cells and factors were associated with treatment failure and decreased overall survival,” Dr Lövgren said.
“We are hoping to follow up this study with another clinical trial that will combine CAR T-cell therapy with chemotherapy known to decrease the number of monocytic myeloid-derived suppressive cells. We are also looking to further optimize the CAR T-cell therapy.”
Dr Lövgren said the main limitations of this study are that it only included 15 patients, the patients had several different malignancies, and some patients may have been too sick to respond to any treatment.
This study was supported by funds from AFA Insurance AB, the Swedish Cancer Society, the Swedish Research Council, the Lions Fund at Uppsala University Hospital, and the Swedish State Support for Clinical Research. Dr Lövgren declared no conflicts of interest.
MAINZ/FRANKFURT, GERMANY—Outcomes of treatment with a third-generation chimeric antigen receptor (CAR) T-cell therapy are associated with a patient’s immune status, according to a phase 1/2a trial.
The CD19-specific CAR T-cell therapy produced a complete response (CR) in 6 of 15 patients with relapsed/refractory CD19-positive leukemia or lymphoma.
Though all responders eventually relapsed, 4 patients—including 2 with stable disease (SD) after treatment—responded to subsequent therapy and are still alive, 1 of them beyond 36 months.
An analysis of blood samples taken throughout the study revealed that a patient’s immune status was associated with treatment failure and overall survival.
Tanja Lövgren, PhD, of Uppsala University in Sweden, and her colleagues presented these findings at the Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (abstract B156).
“CD19-specific CAR T-cell therapy has yielded remarkable response rates for patients who have B-cell acute lymphoblastic leukemia,” Dr Lövgren said. “However, many patients relapse.”
“In addition, response rates are more variable for patients who have other CD19-positive B-cell malignancies, and many patients experience serious adverse events. We set out to investigate the safety and effectiveness of a third-generation CD19-specific CAR T-cell therapy and to identify potential biomarkers of treatment outcome.”
Dr Lövgren and her colleagues studied 15 patients (ages 24-72) who had relapsed or refractory CD19-positive B-cell malignancies:
- Six patients with diffuse large B-cell lymphoma (DLBCL), including 3 cases that were transformed from follicular lymphoma (FL)
- Four patients with pre-B acute lymphoblastic leukemia (ALL)
- Two patients with mantle cell lymphoma (MCL)
- Two patients with chronic lymphocytic leukemia (CLL)
- One patient with FL transformed from Burkitt lymphoma.
Eleven patients received preconditioning with cyclophosphamide (500 mg/m2) and fludarabine (3 doses at 25 mg/m2).
All patients received CAR T cells at 1 x 108, 2 x 107, or 2 x 108 cells/m2. These were autologous, CD19-targeting CAR T cells with 3 intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB.
The researchers assessed tumor responses via bone marrow/blood analysis and/or radiology, depending on the type of malignancy. The team also collected blood samples before CAR T-cell infusion and at multiple times after infusion.
Efficacy and safety
Six patients achieved a CR to treatment—3 with DLBCL (1 transformed), 2 with ALL, and 1 with CLL. Two patients had SD—1 with MCL and 1 with CLL. The remaining patients progressed.
All patients with a CR eventually relapsed. The median duration of CR was 5 months (range, 3-24 months).
Four patients—2 complete responders and 2 with SD—responded well to subsequent therapy and are still alive with 27 to 36 months of follow-up. This includes 1 patient with DLBCL, 1 with MCL, and 2 with CLL.
Four patients had serious adverse events. Three had cytokine-release syndrome, and 2 had neurological toxicity.
All cases of cytokine-release syndrome resolved after treatment with corticosteroids/anti-IL6R therapy. The neurological toxicity resolved spontaneously.
Immune status
An analysis of the blood samples taken throughout the study showed that high levels of monocytic myeloid-derived suppressor cells (MDSCs) prior to treatment was associated with decreased overall survival. In addition, increased levels of MDSCs after treatment preceded treatment failure.
Furthermore, high plasma levels of immunosuppressive factors—such as PD-L1 and PD-L2—after treatment were associated with decreased overall survival.
High plasma levels of biomarkers of an immunostimulatory environment—including IL-12, DC-LAMP, TRAIL, and FasL—before the administration of CAR T-cell therapy was associated with increased overall survival.
“[A]n immunostimulatory environment was associated with improved overall survival, while immunosuppressive cells and factors were associated with treatment failure and decreased overall survival,” Dr Lövgren said.
“We are hoping to follow up this study with another clinical trial that will combine CAR T-cell therapy with chemotherapy known to decrease the number of monocytic myeloid-derived suppressive cells. We are also looking to further optimize the CAR T-cell therapy.”
Dr Lövgren said the main limitations of this study are that it only included 15 patients, the patients had several different malignancies, and some patients may have been too sick to respond to any treatment.
This study was supported by funds from AFA Insurance AB, the Swedish Cancer Society, the Swedish Research Council, the Lions Fund at Uppsala University Hospital, and the Swedish State Support for Clinical Research. Dr Lövgren declared no conflicts of interest.
MAINZ/FRANKFURT, GERMANY—Outcomes of treatment with a third-generation chimeric antigen receptor (CAR) T-cell therapy are associated with a patient’s immune status, according to a phase 1/2a trial.
The CD19-specific CAR T-cell therapy produced a complete response (CR) in 6 of 15 patients with relapsed/refractory CD19-positive leukemia or lymphoma.
Though all responders eventually relapsed, 4 patients—including 2 with stable disease (SD) after treatment—responded to subsequent therapy and are still alive, 1 of them beyond 36 months.
An analysis of blood samples taken throughout the study revealed that a patient’s immune status was associated with treatment failure and overall survival.
Tanja Lövgren, PhD, of Uppsala University in Sweden, and her colleagues presented these findings at the Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (abstract B156).
“CD19-specific CAR T-cell therapy has yielded remarkable response rates for patients who have B-cell acute lymphoblastic leukemia,” Dr Lövgren said. “However, many patients relapse.”
“In addition, response rates are more variable for patients who have other CD19-positive B-cell malignancies, and many patients experience serious adverse events. We set out to investigate the safety and effectiveness of a third-generation CD19-specific CAR T-cell therapy and to identify potential biomarkers of treatment outcome.”
Dr Lövgren and her colleagues studied 15 patients (ages 24-72) who had relapsed or refractory CD19-positive B-cell malignancies:
- Six patients with diffuse large B-cell lymphoma (DLBCL), including 3 cases that were transformed from follicular lymphoma (FL)
- Four patients with pre-B acute lymphoblastic leukemia (ALL)
- Two patients with mantle cell lymphoma (MCL)
- Two patients with chronic lymphocytic leukemia (CLL)
- One patient with FL transformed from Burkitt lymphoma.
Eleven patients received preconditioning with cyclophosphamide (500 mg/m2) and fludarabine (3 doses at 25 mg/m2).
All patients received CAR T cells at 1 x 108, 2 x 107, or 2 x 108 cells/m2. These were autologous, CD19-targeting CAR T cells with 3 intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB.
The researchers assessed tumor responses via bone marrow/blood analysis and/or radiology, depending on the type of malignancy. The team also collected blood samples before CAR T-cell infusion and at multiple times after infusion.
Efficacy and safety
Six patients achieved a CR to treatment—3 with DLBCL (1 transformed), 2 with ALL, and 1 with CLL. Two patients had SD—1 with MCL and 1 with CLL. The remaining patients progressed.
All patients with a CR eventually relapsed. The median duration of CR was 5 months (range, 3-24 months).
Four patients—2 complete responders and 2 with SD—responded well to subsequent therapy and are still alive with 27 to 36 months of follow-up. This includes 1 patient with DLBCL, 1 with MCL, and 2 with CLL.
Four patients had serious adverse events. Three had cytokine-release syndrome, and 2 had neurological toxicity.
All cases of cytokine-release syndrome resolved after treatment with corticosteroids/anti-IL6R therapy. The neurological toxicity resolved spontaneously.
Immune status
An analysis of the blood samples taken throughout the study showed that high levels of monocytic myeloid-derived suppressor cells (MDSCs) prior to treatment was associated with decreased overall survival. In addition, increased levels of MDSCs after treatment preceded treatment failure.
Furthermore, high plasma levels of immunosuppressive factors—such as PD-L1 and PD-L2—after treatment were associated with decreased overall survival.
High plasma levels of biomarkers of an immunostimulatory environment—including IL-12, DC-LAMP, TRAIL, and FasL—before the administration of CAR T-cell therapy was associated with increased overall survival.
“[A]n immunostimulatory environment was associated with improved overall survival, while immunosuppressive cells and factors were associated with treatment failure and decreased overall survival,” Dr Lövgren said.
“We are hoping to follow up this study with another clinical trial that will combine CAR T-cell therapy with chemotherapy known to decrease the number of monocytic myeloid-derived suppressive cells. We are also looking to further optimize the CAR T-cell therapy.”
Dr Lövgren said the main limitations of this study are that it only included 15 patients, the patients had several different malignancies, and some patients may have been too sick to respond to any treatment.
This study was supported by funds from AFA Insurance AB, the Swedish Cancer Society, the Swedish Research Council, the Lions Fund at Uppsala University Hospital, and the Swedish State Support for Clinical Research. Dr Lövgren declared no conflicts of interest.
Biosimilar matches rituximab in large follicular lymphoma trial
MADRID – The biosimilar GP2013 met the criteria for therapeutic equivalence to rituximab in a large comparator trial of previously untreated patients with aggressive follicular lymphoma.
Based on results presented at the European Society for Medical Oncology Congress, “there is absolutely no difference in the objective response rates for GP2013 and rituximab,” the primary endpoint of the trial, reported Wojciech Jurczak, MD, PhD, head of lymphoma, department of hematology, Jagiellonian University, Krakow, Poland.
Dr. Jurczak characterized the double-blind, randomized phase 3 trial ASSIST_FL (NCT01419665) as the “largest biosimilar trial in hematology.” For the study, 629 patients with previously untreated, advanced-stage follicular lymphoma were randomized to GP2013 and the conventional regimen of cyclophosphamide, vincristine, and prednisone (G-CVP) or rituximab and the same three-agent regimen (R-CVP). Each regimen was given for eight cycles followed by maintenance monotherapy with the assigned monoclonal antibody for up to 2 years.
The primary endpoint, objective response rate (ORR), was 87.1% and 87.5% for G-CVP and R-CVP, respectively. There were no differences in ORR among the subgroups evaluated, which included patients aged 60 years and older vs. younger patients, presence or absence of bulky disease, high or low FLIPI (Follicular Lymphoma International Prognostic Index) score, gender, and the geographic region where treatment was given.
Safety was a secondary endpoint evaluated at the end of eight cycles and again after a year of maintenance therapy. The proportion of patients with any adverse event and the proportion with grade 3 or greater adverse events were not statistically different at any time point. There were also no significant differences in any of the other secondary endpoints evaluated, which included pharmacokinetic, pharmacodynamic, and immune measures.
The results are consistent with those of a related randomized bioequivalence trial comparing GP2013 and rituximab in 312 patients with rheumatoid arthritis (Ann Rheum Dis. 2017;76:1598-1602). The primary endpoint in that trial was area-under-the-curve serum concentration time.
The two studies are mutually reinforcing, and “the ASSIST_FL trial ends the story. We have the totality of evidence that GP2013 can be considered a biosimilar,” said Dr. Jurczak, who anticipates “major price differences” for this agent relative to rituximab.
“We may, based on the results of the follicular lymphoma trial, use the biosimilar in all registered indications for rituximab,” said Dr. Jurczak. This is also the conclusion of the European Medicine Agency, which approved this agent in June 2017 for all rituximab indications.
In explaining the process for approval of biosimilars, Dr. Jurczak emphasized that demonstrating bioequivalence is not the same as the approval process for a new therapeutic agent, for which regulatory agents require a demonstration of efficacy on a meaningful clinical endpoint, such as progression-free survival. For biosimilars, it is not necessary to show clinical benefits. Biosimilars must demonstrate the same biological activity, and ORR is considered an acceptable measure.
The ESMO-invited discussant, Michele Ghielmini, MD, PhD, medical director at the Oncology Institute of Southern Switzerland, Bellinzona, agreed. “We can reasonably speculate that (when rituximab and the biosimilar are associated with the same) response rate, they will lead to the same clinical benefits.”
MADRID – The biosimilar GP2013 met the criteria for therapeutic equivalence to rituximab in a large comparator trial of previously untreated patients with aggressive follicular lymphoma.
Based on results presented at the European Society for Medical Oncology Congress, “there is absolutely no difference in the objective response rates for GP2013 and rituximab,” the primary endpoint of the trial, reported Wojciech Jurczak, MD, PhD, head of lymphoma, department of hematology, Jagiellonian University, Krakow, Poland.
Dr. Jurczak characterized the double-blind, randomized phase 3 trial ASSIST_FL (NCT01419665) as the “largest biosimilar trial in hematology.” For the study, 629 patients with previously untreated, advanced-stage follicular lymphoma were randomized to GP2013 and the conventional regimen of cyclophosphamide, vincristine, and prednisone (G-CVP) or rituximab and the same three-agent regimen (R-CVP). Each regimen was given for eight cycles followed by maintenance monotherapy with the assigned monoclonal antibody for up to 2 years.
The primary endpoint, objective response rate (ORR), was 87.1% and 87.5% for G-CVP and R-CVP, respectively. There were no differences in ORR among the subgroups evaluated, which included patients aged 60 years and older vs. younger patients, presence or absence of bulky disease, high or low FLIPI (Follicular Lymphoma International Prognostic Index) score, gender, and the geographic region where treatment was given.
Safety was a secondary endpoint evaluated at the end of eight cycles and again after a year of maintenance therapy. The proportion of patients with any adverse event and the proportion with grade 3 or greater adverse events were not statistically different at any time point. There were also no significant differences in any of the other secondary endpoints evaluated, which included pharmacokinetic, pharmacodynamic, and immune measures.
The results are consistent with those of a related randomized bioequivalence trial comparing GP2013 and rituximab in 312 patients with rheumatoid arthritis (Ann Rheum Dis. 2017;76:1598-1602). The primary endpoint in that trial was area-under-the-curve serum concentration time.
The two studies are mutually reinforcing, and “the ASSIST_FL trial ends the story. We have the totality of evidence that GP2013 can be considered a biosimilar,” said Dr. Jurczak, who anticipates “major price differences” for this agent relative to rituximab.
“We may, based on the results of the follicular lymphoma trial, use the biosimilar in all registered indications for rituximab,” said Dr. Jurczak. This is also the conclusion of the European Medicine Agency, which approved this agent in June 2017 for all rituximab indications.
In explaining the process for approval of biosimilars, Dr. Jurczak emphasized that demonstrating bioequivalence is not the same as the approval process for a new therapeutic agent, for which regulatory agents require a demonstration of efficacy on a meaningful clinical endpoint, such as progression-free survival. For biosimilars, it is not necessary to show clinical benefits. Biosimilars must demonstrate the same biological activity, and ORR is considered an acceptable measure.
The ESMO-invited discussant, Michele Ghielmini, MD, PhD, medical director at the Oncology Institute of Southern Switzerland, Bellinzona, agreed. “We can reasonably speculate that (when rituximab and the biosimilar are associated with the same) response rate, they will lead to the same clinical benefits.”
MADRID – The biosimilar GP2013 met the criteria for therapeutic equivalence to rituximab in a large comparator trial of previously untreated patients with aggressive follicular lymphoma.
Based on results presented at the European Society for Medical Oncology Congress, “there is absolutely no difference in the objective response rates for GP2013 and rituximab,” the primary endpoint of the trial, reported Wojciech Jurczak, MD, PhD, head of lymphoma, department of hematology, Jagiellonian University, Krakow, Poland.
Dr. Jurczak characterized the double-blind, randomized phase 3 trial ASSIST_FL (NCT01419665) as the “largest biosimilar trial in hematology.” For the study, 629 patients with previously untreated, advanced-stage follicular lymphoma were randomized to GP2013 and the conventional regimen of cyclophosphamide, vincristine, and prednisone (G-CVP) or rituximab and the same three-agent regimen (R-CVP). Each regimen was given for eight cycles followed by maintenance monotherapy with the assigned monoclonal antibody for up to 2 years.
The primary endpoint, objective response rate (ORR), was 87.1% and 87.5% for G-CVP and R-CVP, respectively. There were no differences in ORR among the subgroups evaluated, which included patients aged 60 years and older vs. younger patients, presence or absence of bulky disease, high or low FLIPI (Follicular Lymphoma International Prognostic Index) score, gender, and the geographic region where treatment was given.
Safety was a secondary endpoint evaluated at the end of eight cycles and again after a year of maintenance therapy. The proportion of patients with any adverse event and the proportion with grade 3 or greater adverse events were not statistically different at any time point. There were also no significant differences in any of the other secondary endpoints evaluated, which included pharmacokinetic, pharmacodynamic, and immune measures.
The results are consistent with those of a related randomized bioequivalence trial comparing GP2013 and rituximab in 312 patients with rheumatoid arthritis (Ann Rheum Dis. 2017;76:1598-1602). The primary endpoint in that trial was area-under-the-curve serum concentration time.
The two studies are mutually reinforcing, and “the ASSIST_FL trial ends the story. We have the totality of evidence that GP2013 can be considered a biosimilar,” said Dr. Jurczak, who anticipates “major price differences” for this agent relative to rituximab.
“We may, based on the results of the follicular lymphoma trial, use the biosimilar in all registered indications for rituximab,” said Dr. Jurczak. This is also the conclusion of the European Medicine Agency, which approved this agent in June 2017 for all rituximab indications.
In explaining the process for approval of biosimilars, Dr. Jurczak emphasized that demonstrating bioequivalence is not the same as the approval process for a new therapeutic agent, for which regulatory agents require a demonstration of efficacy on a meaningful clinical endpoint, such as progression-free survival. For biosimilars, it is not necessary to show clinical benefits. Biosimilars must demonstrate the same biological activity, and ORR is considered an acceptable measure.
The ESMO-invited discussant, Michele Ghielmini, MD, PhD, medical director at the Oncology Institute of Southern Switzerland, Bellinzona, agreed. “We can reasonably speculate that (when rituximab and the biosimilar are associated with the same) response rate, they will lead to the same clinical benefits.”
AT ESMO 2017
Key clinical point:
Major finding: The objective response rates were 87.1% and 87.5% for G-CVP and R-CVP.
Data source: Double-blind, multicenter randomized trial of 629 patients with previously untreated, advanced-stage follicular lymphoma.
Disclosures: Dr. Jurczak reported financial relationships with Sandoz.
Biosimilar deemed equivalent to reference drug in FL
MADRID—The biosimilar GP2013 has demonstrated equivalence to its reference drug rituximab in patients with previously untreated, advanced-stage follicular lymphoma (FL), according to researchers.
Treatment with GP2013 plus cyclophosphamide, vincristine, and prednisone (CVP) produced a similar overall response rate (ORR) as rituximab plus CVP in the phase 3 ASSIST-FL trial.
Survival rates were also similar between the treatment arms, as were adverse events (AEs).
Results from this study were published in The Lancet Haematology and presented at ESMO 2017 Congress (abstract 994O).
The study was funded by Hexal AG, a Sandoz company (part of the Novartis group), which is marketing GP2013 as Rixathon in Europe.
Patients and treatment
The trial included 629 patients with previously untreated, advanced-stage FL. They were randomized to receive 8 cycles of GP2013-CVP (n=314) or rituximab-CVP (n=315). Responders in either arm could receive monotherapy maintenance for up to 2 years.
The mean age was 57.5 in the GP2013 arm and 56.4 in the rituximab arm. Fifty-eight percent and 54% of patients, respectively, were female.
Fifty-seven percent of patients in the GP2013 arm and 56% in the rituximab arm had an ECOG performance status of 0. Forty percent and 39%, respectively, had a status of 1. Two percent and 4%, respectively, had a status of 2. (For the remaining 1% of patients in each arm, data on performance status were missing.)
Patients had an Ann Arbor stage of III—46% in the GP2013 arm and 43% in the GP2013 arm—or IV—54% in the GP2013 arm and 57% in the rituximab arm.
Fifty-six percent of patients in each arm were high-risk according to FLIPI. Thirty-four percent in the GP2013 arm and 33% in the rituximab arm were intermediate-risk. Ten percent and 11%, respectively, were low-risk.
Fourteen percent of patients in the GP2013 arm and 18% in the rituximab arm had bulky disease. Fifteen percent and 13%, respectively, had splenic involvement.
ORR and survival
The patients had a median follow-up of 23.8 months. The primary efficacy endpoint was equivalence in ORR, defined by a 95% confidence interval (CI) with a margin of ± 12% standard deviation.
The primary endpoint was met, as the ORR was 87% in the GP2013 arm and 88% in the rituximab arm, with a difference of –0.40% (95% CI –5.94%, 5.14%).
The complete response rate was 15% in the GP2013 arm and 13% in the rituximab arm. The partial response rates were 72% and 74%, respectively.
The median progression-free survival and overall survival have not been reached. However, the progression-free survival rate was 70% in the GP2013 arm and 76% in the rituximab arm (hazard ratio [HR]=1.31; 95% CI 1.02, 1.69).
The overall survival rate was 93% in the GP2013 arm and 91% in the rituximab arm (HR=0.77; 95% CI 0.49, 1.22).
Safety
During the combination phase, the incidence of AEs was 93% in the GP2013 arm and 91% in the rituximab arm. The incidence of serious AEs was 23% and 20%, respectively.
The most frequent AEs (in the GP2013 and rituximab arms, respectively) were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%). The most common grade 3/4 AE was neutropenia (18% and 21%).
There were 11 deaths reported during the combination phase—4 in the GP2013 arm and 7 in the rituximab arm.
Three deaths in the GP2013 arm (sudden death, septic shock, and respiratory failure) and 2 deaths in the rituximab arm (multiple organ dysfunction syndrome and sepsis) were suspected to be related to study treatment.
During the maintenance phase, the incidence of AEs was 63% in the GP2013 arm and 57% in the rituximab arm. The incidence of serious AEs was 6% and 4%, respectively.
The most frequent AEs (in the GP2013 and rituximab arms, respectively) were infections and infestations (20% and 27%), neutropenia (10% and 6%), cough (9% and 6%), and upper respiratory tract infection (3% and 6%). The most common grade 3/4 AE was neutropenia (7% and 4%).
There were 4 deaths reported during the maintenance phase, 2 in each treatment arm.
MADRID—The biosimilar GP2013 has demonstrated equivalence to its reference drug rituximab in patients with previously untreated, advanced-stage follicular lymphoma (FL), according to researchers.
Treatment with GP2013 plus cyclophosphamide, vincristine, and prednisone (CVP) produced a similar overall response rate (ORR) as rituximab plus CVP in the phase 3 ASSIST-FL trial.
Survival rates were also similar between the treatment arms, as were adverse events (AEs).
Results from this study were published in The Lancet Haematology and presented at ESMO 2017 Congress (abstract 994O).
The study was funded by Hexal AG, a Sandoz company (part of the Novartis group), which is marketing GP2013 as Rixathon in Europe.
Patients and treatment
The trial included 629 patients with previously untreated, advanced-stage FL. They were randomized to receive 8 cycles of GP2013-CVP (n=314) or rituximab-CVP (n=315). Responders in either arm could receive monotherapy maintenance for up to 2 years.
The mean age was 57.5 in the GP2013 arm and 56.4 in the rituximab arm. Fifty-eight percent and 54% of patients, respectively, were female.
Fifty-seven percent of patients in the GP2013 arm and 56% in the rituximab arm had an ECOG performance status of 0. Forty percent and 39%, respectively, had a status of 1. Two percent and 4%, respectively, had a status of 2. (For the remaining 1% of patients in each arm, data on performance status were missing.)
Patients had an Ann Arbor stage of III—46% in the GP2013 arm and 43% in the GP2013 arm—or IV—54% in the GP2013 arm and 57% in the rituximab arm.
Fifty-six percent of patients in each arm were high-risk according to FLIPI. Thirty-four percent in the GP2013 arm and 33% in the rituximab arm were intermediate-risk. Ten percent and 11%, respectively, were low-risk.
Fourteen percent of patients in the GP2013 arm and 18% in the rituximab arm had bulky disease. Fifteen percent and 13%, respectively, had splenic involvement.
ORR and survival
The patients had a median follow-up of 23.8 months. The primary efficacy endpoint was equivalence in ORR, defined by a 95% confidence interval (CI) with a margin of ± 12% standard deviation.
The primary endpoint was met, as the ORR was 87% in the GP2013 arm and 88% in the rituximab arm, with a difference of –0.40% (95% CI –5.94%, 5.14%).
The complete response rate was 15% in the GP2013 arm and 13% in the rituximab arm. The partial response rates were 72% and 74%, respectively.
The median progression-free survival and overall survival have not been reached. However, the progression-free survival rate was 70% in the GP2013 arm and 76% in the rituximab arm (hazard ratio [HR]=1.31; 95% CI 1.02, 1.69).
The overall survival rate was 93% in the GP2013 arm and 91% in the rituximab arm (HR=0.77; 95% CI 0.49, 1.22).
Safety
During the combination phase, the incidence of AEs was 93% in the GP2013 arm and 91% in the rituximab arm. The incidence of serious AEs was 23% and 20%, respectively.
The most frequent AEs (in the GP2013 and rituximab arms, respectively) were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%). The most common grade 3/4 AE was neutropenia (18% and 21%).
There were 11 deaths reported during the combination phase—4 in the GP2013 arm and 7 in the rituximab arm.
Three deaths in the GP2013 arm (sudden death, septic shock, and respiratory failure) and 2 deaths in the rituximab arm (multiple organ dysfunction syndrome and sepsis) were suspected to be related to study treatment.
During the maintenance phase, the incidence of AEs was 63% in the GP2013 arm and 57% in the rituximab arm. The incidence of serious AEs was 6% and 4%, respectively.
The most frequent AEs (in the GP2013 and rituximab arms, respectively) were infections and infestations (20% and 27%), neutropenia (10% and 6%), cough (9% and 6%), and upper respiratory tract infection (3% and 6%). The most common grade 3/4 AE was neutropenia (7% and 4%).
There were 4 deaths reported during the maintenance phase, 2 in each treatment arm.
MADRID—The biosimilar GP2013 has demonstrated equivalence to its reference drug rituximab in patients with previously untreated, advanced-stage follicular lymphoma (FL), according to researchers.
Treatment with GP2013 plus cyclophosphamide, vincristine, and prednisone (CVP) produced a similar overall response rate (ORR) as rituximab plus CVP in the phase 3 ASSIST-FL trial.
Survival rates were also similar between the treatment arms, as were adverse events (AEs).
Results from this study were published in The Lancet Haematology and presented at ESMO 2017 Congress (abstract 994O).
The study was funded by Hexal AG, a Sandoz company (part of the Novartis group), which is marketing GP2013 as Rixathon in Europe.
Patients and treatment
The trial included 629 patients with previously untreated, advanced-stage FL. They were randomized to receive 8 cycles of GP2013-CVP (n=314) or rituximab-CVP (n=315). Responders in either arm could receive monotherapy maintenance for up to 2 years.
The mean age was 57.5 in the GP2013 arm and 56.4 in the rituximab arm. Fifty-eight percent and 54% of patients, respectively, were female.
Fifty-seven percent of patients in the GP2013 arm and 56% in the rituximab arm had an ECOG performance status of 0. Forty percent and 39%, respectively, had a status of 1. Two percent and 4%, respectively, had a status of 2. (For the remaining 1% of patients in each arm, data on performance status were missing.)
Patients had an Ann Arbor stage of III—46% in the GP2013 arm and 43% in the GP2013 arm—or IV—54% in the GP2013 arm and 57% in the rituximab arm.
Fifty-six percent of patients in each arm were high-risk according to FLIPI. Thirty-four percent in the GP2013 arm and 33% in the rituximab arm were intermediate-risk. Ten percent and 11%, respectively, were low-risk.
Fourteen percent of patients in the GP2013 arm and 18% in the rituximab arm had bulky disease. Fifteen percent and 13%, respectively, had splenic involvement.
ORR and survival
The patients had a median follow-up of 23.8 months. The primary efficacy endpoint was equivalence in ORR, defined by a 95% confidence interval (CI) with a margin of ± 12% standard deviation.
The primary endpoint was met, as the ORR was 87% in the GP2013 arm and 88% in the rituximab arm, with a difference of –0.40% (95% CI –5.94%, 5.14%).
The complete response rate was 15% in the GP2013 arm and 13% in the rituximab arm. The partial response rates were 72% and 74%, respectively.
The median progression-free survival and overall survival have not been reached. However, the progression-free survival rate was 70% in the GP2013 arm and 76% in the rituximab arm (hazard ratio [HR]=1.31; 95% CI 1.02, 1.69).
The overall survival rate was 93% in the GP2013 arm and 91% in the rituximab arm (HR=0.77; 95% CI 0.49, 1.22).
Safety
During the combination phase, the incidence of AEs was 93% in the GP2013 arm and 91% in the rituximab arm. The incidence of serious AEs was 23% and 20%, respectively.
The most frequent AEs (in the GP2013 and rituximab arms, respectively) were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%). The most common grade 3/4 AE was neutropenia (18% and 21%).
There were 11 deaths reported during the combination phase—4 in the GP2013 arm and 7 in the rituximab arm.
Three deaths in the GP2013 arm (sudden death, septic shock, and respiratory failure) and 2 deaths in the rituximab arm (multiple organ dysfunction syndrome and sepsis) were suspected to be related to study treatment.
During the maintenance phase, the incidence of AEs was 63% in the GP2013 arm and 57% in the rituximab arm. The incidence of serious AEs was 6% and 4%, respectively.
The most frequent AEs (in the GP2013 and rituximab arms, respectively) were infections and infestations (20% and 27%), neutropenia (10% and 6%), cough (9% and 6%), and upper respiratory tract infection (3% and 6%). The most common grade 3/4 AE was neutropenia (7% and 4%).
There were 4 deaths reported during the maintenance phase, 2 in each treatment arm.
FDA grants Priority Review to Gazyva for follicular lymphoma
Gazyva (obinutuzumab) has been granted a Priority Review by the Food and Drug Administration for the treatment of previously untreated follicular lymphoma, according to a press release from Genentech.
FDA approval was based on results from the GALLIUM study, a phase 3 trial comparing Gazyva to Rituxan (rituximab). Patients who received Gazyva plus chemotherapy followed by Gazyva therapy alone for 2 years had a 32% improvement in progression-free survival during the 41.1 month follow-up period, compared with the patient group who received Rituxan plus chemotherapy followed by 2 years of Rituxan therapy alone. Median progression-free survival has not been reached in either arm of the study.
The most common adverse events that occurred more often in the Gazyva arm of the study were low white blood cell count, infections, infusion-related reactions, low platelet count, new tumors, and cardiac events.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible,” Dr. Sandra Horning, chief medical officer and head of Genentech’s Global Product Development said in the press release.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017.
Find the full press release on the Genentech website.
Gazyva (obinutuzumab) has been granted a Priority Review by the Food and Drug Administration for the treatment of previously untreated follicular lymphoma, according to a press release from Genentech.
FDA approval was based on results from the GALLIUM study, a phase 3 trial comparing Gazyva to Rituxan (rituximab). Patients who received Gazyva plus chemotherapy followed by Gazyva therapy alone for 2 years had a 32% improvement in progression-free survival during the 41.1 month follow-up period, compared with the patient group who received Rituxan plus chemotherapy followed by 2 years of Rituxan therapy alone. Median progression-free survival has not been reached in either arm of the study.
The most common adverse events that occurred more often in the Gazyva arm of the study were low white blood cell count, infections, infusion-related reactions, low platelet count, new tumors, and cardiac events.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible,” Dr. Sandra Horning, chief medical officer and head of Genentech’s Global Product Development said in the press release.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017.
Find the full press release on the Genentech website.
Gazyva (obinutuzumab) has been granted a Priority Review by the Food and Drug Administration for the treatment of previously untreated follicular lymphoma, according to a press release from Genentech.
FDA approval was based on results from the GALLIUM study, a phase 3 trial comparing Gazyva to Rituxan (rituximab). Patients who received Gazyva plus chemotherapy followed by Gazyva therapy alone for 2 years had a 32% improvement in progression-free survival during the 41.1 month follow-up period, compared with the patient group who received Rituxan plus chemotherapy followed by 2 years of Rituxan therapy alone. Median progression-free survival has not been reached in either arm of the study.
The most common adverse events that occurred more often in the Gazyva arm of the study were low white blood cell count, infections, infusion-related reactions, low platelet count, new tumors, and cardiac events.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible,” Dr. Sandra Horning, chief medical officer and head of Genentech’s Global Product Development said in the press release.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017.
Find the full press release on the Genentech website.
Drug receives priority review for FL
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).
With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.
The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.
About obinutuzumab
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.
The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.
About the GALLIUM study
GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with 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.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).
With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.
The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.
About obinutuzumab
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.
The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.
About the GALLIUM study
GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with 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.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).
The US Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application (sBLA) for obinutuzumab (Gazyva®).
With this sBLA, Genentech is seeking approval for obinutuzumab to be used, first in combination with chemotherapy and then alone as maintenance, in patients with previously untreated follicular lymphoma (FL).
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The FDA plans to make a decision on the sBLA for obinutuzumab by December 23, 2017.
The sBLA is supported by results of the GALLIUM study, which were presented at the 2016 ASH Annual Meeting.
About obinutuzumab
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug is FDA-approved for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Obinutuzumab is also approved to treat FL patients who relapse after, or are refractory to, a rituximab-containing regimen. In these patients, obinutuzumab is given first in combination with bendamustine and then alone as maintenance.
The full prescribing information for obinutuzumab is available at http://www.Gazyva.com.
About the GALLIUM study
GALLIUM enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with 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.
Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).
There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).
The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.
The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.
Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).