Obinutuzumab for the First-Line Treatment of Follicular Lymphoma
Background
Rituximab-based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. We compared rituximab-based chemotherapy with obinutuzumab-based chemotherapy in patients with previously untreated advanced-stage follicular lymphoma.
Methods
We randomly assigned patients to undergo induction treatment with obinutuzumab-based chemotherapy or rituximab-based chemotherapy. Patients with a response received maintenance treatment for up to 2 years with the same antibody that they had received in induction. The primary end point was investigator-assessed progression-free survival.
Results
A total of 1202 patients with follicular lymphoma underwent randomization (601 patients in each group). After a median follow-up of 34.5 months (range, 0 to 54.5), a planned interim analysis showed that obinutuzumab-based chemotherapy resulted in a significantly lower risk of progression, relapse, or death than rituximab-based chemotherapy (estimated 3-year rate of progression-free survival, 80.0% vs. 73.3%; hazard ratio for progression, relapse, or death, 0.66; 95% confidence interval [CI], 0.51 to 0.85; P=0.001). Similar results were seen with regard to independently reviewed progression-free survival and other time-to-event end points. Response rates were similar in the two groups (88.5% in the obinutuzumab group and 86.9% in the rituximab group). Adverse events of grade 3 to 5 were more frequent in the obinutuzumab group than in the rituximab group (74.6% vs. 67.8%), as were serious adverse events (46.1% vs. 39.9%). The rates of adverse events resulting in death were similar in the two groups (4.0% in the obinutuzumab group and 3.4% in the rituximab group). The most common adverse events were infusion-related events that were considered by the investigators to be largely due to obinutuzumab in 353 of 595 patients (59.3%; 95% CI, 55.3 to 63.2) and to rituximab in 292 of 597 patients (48.9%; 95% CI, 44.9 to 52.9; P<0.001). Nausea and neutropenia were common. A total of 35 patients (5.8%) in the obinutuzumab group and 46 (7.7%) in the rituximab group died.
Conclusions
Obinutuzumab-based immunochemotherapy and maintenance therapy resulted in longer progression-free survival than rituximab-based therapy. High-grade adverse events were more common with obinutuzumab-based chemotherapy. (Funded by F. Hoffmann–La Roche; GALLIUM ClinicalTrials.gov number, NCT01332968.)
Supported by F. Hoffmann–La Roche.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Dr. Marcus reports receiving consulting fees and lecture fees from Takeda Pharmaceuticals and travel support, consulting fees, and lecture fees from Roche; Dr. Davies, receiving honoraria from Mundipharma and Janssen, grant support, honoraria, consulting fees, and advisory fees from Gilead Sciences, consulting fees and advisory fees from Takeda Pharmaceuticals, and research funding from Bayer, Celgene, and GlaxoSmithKline; Dr. Klapper, receiving grant support from Novartis, Amgen, and Bayer; Dr. Opat, receiving research funding, advisory fees, speaker’s fees, honoraria, and provision of subsidized drugs from Roche, Janssen, and Celgene, research funding, advisory fees, speaker’s fees, and honoraria from Takeda Pharmaceuticals and Novartis, research funding, advisory fees, and honoraria from AbbVie and Gilead Sciences, advisory fees and travel support from Bristol-Myers Squibb, research funding from BeiGene, and advisory fees from Sanofi and Mundipharma; Dr. Owen, receiving grant support and honoraria from Roche, Gilead Sciences, Celgene, and Lundbeck, honoraria from Janssen, AbbVie, and Novartis, and grant support from Pharmacyclics; Dr. Sangha, receiving honoraria from Pfizer and Lundbeck and receiving honoraria from and serving as a member of the advisory board and the board of directors for Boehringer Ingelheim, AstraZeneca, Roche, Eli Lilly, Bristol-Myers Squibb, and Merck; Dr. Seymour, receiving grant support, honoraria, consulting fees, and advisory fees from AbbVie and Janssen, honoraria, consulting fees, advisory fees, and travel support from Celgene and Roche, and honoraria, consulting fees, and advisory fees from Genentech,
-Abstract Truncated-
Publisher URL: http://www.nejm.org/doi/full/10.1056/NEJMoa1614598
DOI: 10.1056/NEJMoa1614598
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