The US Food and Drug Administration (FDA) announced today that it has approved obinutuzumab (Gazyva, Genentech) for use in follicular lymphoma, the most common type of indolent non-Hodgkin's lymphoma (NHL).
This is the second FDA approval for obinutuzumab. The drug received the green light in 2013 for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia.
The new indication is for obinutuzumab to be combined with bendamustine chemotherapy followed by treatment with obinutuzumab alone in patients with follicular lymphoma who failed to respond to a regimen containing rituximab (Rituxan, Genentech), or for patients whose follicular lymphoma relapsed receiving that treatment.
"People with follicular lymphoma whose disease returns or worsens despite treatment with a rituximab-containing regimen need more options because the disease becomes more difficult to treat each time it comes back," said Sandra Horning, MD, chief medical officer and head of global product development at Genentech.
"Obinutuzumab plus bendamustine provides a new treatment option that can be used after relapse to significantly reduce the risk of progression or death," Dr Horning said in a statement.
Obinutuzumab is a humanized anti-CD20 monoclonal antibody of the IgG1 subclass that recognizes a specific epitope of the CD20 molecule found on B-cells. It attacks targeted cells both directly and together with the body's immune system.
Improved Progression-Free Survival
The approval for the new indication of follicular lymphoma is based on data from the phase 3 GADOLIN study, which showed that obinutuzumab plus bendamustine followed by obinutuzumab alone led to a 52% reduction in progression-free survival in patients with relapsed disease, compared with bendamustine alone.
The GADOLIN study evaluated the use of obinutuzumab plus bendamustine followed by obinutuzumab alone until disease progression or for up to 2 years, and compared it with bendamustine used alone. The cohort involved 413 patients with indolent NHL — 321 with follicular lymphoma — whose disease progressed during or within 6 months of previous rituximab-based therapy.
The obinutuzumab regimen improved progression-free survival compared with bendamustine alone (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.34 - 0.68; P < .0001). Median progression-free survival was not reached in the obinutuzumab group, but was 13.8 months in the group receiving bendamustine alone.
As assessed by investigator review, median progression-free survival with obinutuzumab was more than double that with bendamustine alone (29.2 vs 13.7 months; HR, 0.48; 95% CI, 0.35 - 0.67; P < .0001).
The trial was stopped early after a planned interim analysis showed efficacy. When the results were presented last year, Merry-Jennifer Markham, MD, a hematologist/oncologist from the University of Florida in Gainesville, said: "It's encouraging to see such impressive results for a novel anti-CD20 monoclonal antibody in a difficult-to-treat patient population such as those with rituximab-refractory indolent non-Hodgkin's lymphoma."
"The fact that this approach stalled cancer progression by more than a year will be good news to patients, who urgently need additional treatment options," she added. The risk for death was reduced by 38% in the obinutuzumab cohort, versus bendamustine alone, based on a post hoc analysis with 24.1 months of median observation time (HR, 0.62).
The median overall survival has not yet been reached in either study group.
The most common grade 3/4 hematologic adverse events included neutropenia (in 33.0% of the combination group and 26.3% of the monotherapy group), thrombocytopenia (10.8% vs 16.2%), anemia (7.7% vs 10.1%), febrile neutropenia (4.6% vs 3.5%), and leukopenia (1.0% vs 1.5%).
The most common nonhematologic adverse events included vomiting, decreased appetite, and fatigue.
The manufacturer indicates that obinutuzumab is currently being studied for other indications in the ongoing phase 3 studies. The GOYA trial is comparing obintuzumab head-to-head with rituxumab plus CHOP chemotherapy in first-line diffuse large B-cell lymphoma, and GALLIUM is comparing obintuzumab plus chemotherapy head-to-head with rituxumab plus chemotherapy in first-line indolent NHL.
Additional combination studies investigating the agent with other approved or investigational medicines, including cancer immunotherapies and small-molecule inhibitors, are planned or underway across a range of blood cancers, according to Genentech.
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Cite this: FDA Okay for Obinutuzumab for Follicular Lymphoma - Medscape - Feb 26, 2016.
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