Obinutuzumab and bendamustine followed by obinutuzumab maintenance therapy was superior to bendamustine monotherapy based on progression-free survival in rituximab-refractory patients with indolent non-Hodgkin lymphoma, based on a study published online in the Lancet Oncology.
After a median follow-up of 22 months in the obinutuzumab plus bendamustine group and 20 months in the bendamustine monotherapy group, progression-free survival was significantly longer with obinutuzumab plus bendamustine (median not reached; 95% confidence interval, 22.5 months – not estimable) than with bendamustine monotherapy (14.9 months, range, 12.8-16.6; hazard ratio, 0.55; 95% CI 0.40-0.74; P = .0001). About two-thirds of the nearly 400 patients in both study arms had grade 3-5 adverse events.
The anti-CD20 monoclonal antibody obinutuzumab is an option when patients with indolent non-Hodgkin lymphoma relapse or don’t achieve adequate disease control with rituximab-based treatment, wrote Laurie H. Sehn, MD, of the British Columbia Cancer Agency and the University of British Columbia, Vancouver, and her colleagues.
In an open-label, randomized, phase III study called GADOLIN, patients with CD20-positive indolent non-Hodgkin lymphoma were stratified by indolent non-Hodgkin lymphoma subtype, rituximab-refractory type, number of previous therapies, and geographic region.
For the study, 194 patients were assigned to obinutuzumab plus bendamustine and 202 to bendamustine monotherapy. Trial participants received six 28-day cycles with either obinutuzumab plus bendamustine (obinutuzumab 1,000 mg on days 1, 8, and 15, cycle 1; and on day 1, cycles 2-6) plus bendamustine (90 mg/m2 per day on days 1 and 2, cycles 1-6) or bendamustine monotherapy (120 mg/m2 per day on days 1 and 2 of all cycles). Patients in the obinutuzumab plus bendamustine group whose disease did not progress received obinutuzumab maintenance therapy of 1,000 mg once every 2 months for up to 2 years.
Grade 3-5 adverse events occurred in 68% of 194 patients in the obinutuzumab plus bendamustine group and in 62% of 198 patients in the bendamustine monotherapy group. Grade 3 or worse neutropenia affected 33% of the obinutuzumab plus bendamustine group and 26% of the bendamustine monotherapy group. Other grade 3 or worse events included thrombocytopenia in 11% and 16%, anemia in 8% and 10%, and infusion-related reactions in 11% and 6%. Serious adverse events occurred in 38% in the obinutuzumab plus bendamustine group and in 33% in the bendamustine monotherapy group. Adverse events resulted in death in 6% of patients in each group.
The study was funded by Hoffmann-La Roche. Genentech, the maker of obinutuzumab (Gazyva) in the United States, is a wholly owned member of the Roche Group. Dr. Sehn receives honoraria and is a consultant or advisor to Genentech as well as several other drug companies.
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