Obinutuzumab for the First-Line Treatment of Follicular Lymphoma.

Abstract

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 .).

• Authors: Robert Marcus, Andrew Davies, Kiyoshi Ando, Wolfram Klapper, Stephen Opat, Carolyn Owen, Elizabeth Phillips, Randeep Sangha, Rudolf Schlag, John F Seymour, William Townsend, Marek Trněný, Michael Wenger, Günter Fingerle-Rowson, Kaspar Rufibach, Tom Moore, Michael Herold, Wolfgang Hiddemann
• Journal: The New England journal of medicine (N Engl J Med) Vol. 377 Issue 14 Pg. 1331-1344 (10 05 2017) ISSN: 1533-4406 [Electronic] United States
• PMID: 28976863 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Immunologic Factors
• Rituximab
• obinutuzumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Agents (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Disease-Free Survival
• Female
• Humans
• Immunologic Factors (administration & dosage, adverse effects)
• Induction Chemotherapy
• Kaplan-Meier Estimate
• Leukopenia (chemically induced)
• Lymphoma, Follicular (drug therapy, mortality)
• Male
• Middle Aged
• Nausea (chemically induced)
• Rituximab (administration & dosage, adverse effects)