On November 16, 2017, the Food and Drug Administration granted regular approval to obinutuzumab (GAZYVA, Genentech, Inc.) in combination with chemotherapy, followed by obinutuzumab monotherapy in patients achieving at least a partial remission, for the treatment of adult patients with previously untreated stage II bulky, III, or IV follicular lymphoma (FL).
Approval was based on a multicenter, open-label, randomized phase 3 trial (GALLIUM) for patients with previously untreated non-Hodgkin lymphoma, including 1202 patients with FL. Patients were randomized 1:1 to receive either obinutuzumab + chemotherapy or rituximab + chemotherapy, followed in responding patients by obinutuzumab or rituximab maintenance for up to 2 years. Of the patients with FL, 91% had stage III-IV disease, 44% had bulky disease, and 79% had at least intermediate-risk disease. The chemotherapy backbone was bendamustine in 57%, CHOP in 33% and CVP in 10%. With a median follow-up of 38 months, progression-free survival, as assessed by an independent review committee, was statistically significantly improved in the obinutuzumab arm, with an estimated hazard ratio of 0.72 (95% CI: 0.56, 0.93; p=0.0118) compared to the rituximab arm. Median progression-free survival was not reached in either arm. As assessed by CT, the arms had similar overall response rates (91% with obinutuzumab, 88% with rituximab) and complete remission rates (28% and 27%, respectively).
Among the 1385 patients evaluated for safety, the obinutuzumab arm had higher incidences of serious adverse reactions (ARs; 50% compared to 43% in the rituximab arm), grade ≥ 3 ARs (79% vs. 72%) and fatal infections (2% vs.
In patients with previously untreated FL, the recommended dose-schedule of obinutuzumab is 1000 mg intravenously on days 1, 8 and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6 or cycles 2-8; and then 1000 mg every 2 months for up to 2 years.
Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125486s017s018lbl.pdf.
FDA granted priority review to obinutuzumab for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
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