August 2015, Vol 4, No 4
GADOLIN Trial: Obinutuzumab Moves into Indolent Lymphoma
Results from the phase 3 GADOLIN trial provide the first proof of efficacy for obinutuzumab in indolent non-Hodgkin lymphoma (NHL). Obinutuzumab added to standard bendamustine chemotherapy more than doubled progression-free survival (PFS) in patients with rituximab-refractory indolent lymphoma: median PFS was 29.2 months with obinutuzumab/bendamustine versus 14 months with bendamustine alone. Because of these results, the study was stopped early.
“Indolent NHL is incurable with standard therapy. Rituximab improves overall survival and progression-free survival, but some patients do not respond to rituximab, and others relapse on rituximab, and these patients have a poor outcome,” explained lead author Laurie Sehn, MD, BC Cancer Agency and the University of British Columbia, Vancouver, Canada.
“This study is a remarkable first demonstration of a novel antibody for patients who are rituximab refractory. Results are statistically significant and clinically meaningful, with no new safety signals. Based on these results, bendamustine plus obinutuzumab followed by obinutuzumab maintenance is a novel and effective treatment option for patients with indolent NHL refractory to rituximab,” she stated.
The prospective, phase 3 GADOLIN trial randomized 413 patients to obinutuzumab/bendamustine followed by obinutuzumab maintenance versus bendamustine and placebo maintenance. In the combination arm, bendamustine was dosed at 90 mg/m2, a flat dose used in combination with other drugs. In the monotherapy arm, the dose was 120 mg/m2 for up to 6 cycles.
Demographic and clinical characteristics were comparable in both arms of the trial. Median age was 63 years, with a median of 2 prior lines of therapy. More than 90% of patients in each arm were refractory to their last therapy.
The study met its primary end point at a preplanned interim analysis.
Median PFS was 14.9 months for bendamustine versus not yet reached in the combination arm, for a 45% reduction in the rate of progression. Investigator-assessed PFS and PFS assessed by an independent review committee were similar.
The rate of adverse events was similar in the treatment arms. Grade 3 or higher adverse events, deaths, and withdrawal from therapy were also similar.
No new safety signals emerged for either drug. Side effects were as expected. The most frequently reported hematologic toxicities were neutropenia (35% for the combination and 29% for bendamustine alone) and thrombocytopenia (15% vs 24%, respectively). The most common nonhematologic toxicities were infusion-related reactions (69% vs 63%, respectively), nausea (54% vs 61%, respectively), fatigue (39% vs 33%, respectively), and diarrhea (27% vs 30%, respectively).
“Most patients with indolent NHL will become refractory to rituximab. These robust results are preliminary, but they open doors to therapies that will give these patients with an incurable disease more time,” said Jennifer Markham, MD, University of Florida, Gainesville.
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