Chicago, IL—The results of the phase 3 GADOLIN trial provide the first proof of efficacy for obinutuzumab (Gazyva) in patients with indolent non-Hodgkin lymphoma (NHL). Obinutuzumab added to standard bendamustine (Treanda) chemotherapy almost doubled progression-free survival (PFS) in patients with rituximab (Rituximab)-refractory indolent lymphoma—the median PFS was 29.2 months with obinutuzumab plus bendamustine versus 14 months with bendamustine alone.
As a result of these findings, the study was stopped early. The findings were presented at the 2015 American Society of Clinical Oncology (ASCO) meeting.
“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,” said lead investigator Laurie H. Sehn, MD, MPH, BSc, a medical oncologist at BC Cancer Agency, Vancouver, British Columbia, Canada.
“This study is a remarkable first demonstration of a novel antibody for patients who are rituximab-refractory. The 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,” Dr Sehn stated.
The prospective, phase 3 GADOLIN trial randomized 413 patients to obinutuzumab plus 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.
The demographic and clinical characteristics were comparable in both arms of the trial. The patients’ median age was 63 years, with a median of 2 previous lines of therapy. More than 90% of the patients in each arm had disease refractory to their last therapy.
The study met its primary end point at a preplanned interim analysis.
The median PFS was 14.9 months for the patients receiving the bendamustine plus obinutuzumab arm and the PFS was not yet reached in the arm receiving bendamustine alone—a 45% reduction in the rate of disease progression. The investigator-assessed PFS and the PFS assessed by an Independent Review Committee were similar.
The rates of adverse events were similar in both treatment arms. Grade ?3 adverse events, deaths, and withdrawal from therapy were also similar.
No new safety signals emerged for either drug.
“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 ASCO expert Merry Jennifer Markham, MD, Assistant Professor of Medicine, University of Florida, Gainesville.
