Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study.

peer reviewedABSTRACT Background: Lenalidomide plus rituximab can treat patients with relapsed/refractory follicular lymphoma. Obinutuzumab enhances antibody-dependent cellular cytotoxicity, phagocytosis, and direct B-cell killing better than rituximab. Our aim was to determine efficacy and safety of lenalidomide plus obinutuzumab for treating relapsed/refractory follicular lymphoma. Methods: This is an ongoing, phase 2, open-label, multicenter study of patients with CD20- positive, relapsed/refractory follicular lymphoma (≥1 previous rituximab-containing regimen). Patients received oral lenalidomide 20 mg plus IV-infused obinutuzumab 1000 mg (six 28-day cycles; induction), 1-year maintenance with lenalidomide 10 mg ([12] 28-day cycles; days 2–22) plus obinutuzumab 1000 mg (alternate cycles), and 1-year maintenance with obinutuzumab 1000 mg (six 56-day cycles; day 1). Primary endpoint was overall response rate (ORR) at induction end per 1999 International Working Group criteria. Adverse events (AEs) were monitored. Findings: Eighty-six patients were evaluable for efficacy (88 for safety). ORR at induction end was 79·1% (95% CI, 68·9−87·1), meeting the pre-specified primary endpoint. Median follow-up for survival was 2·6 years (interquartile range, 2·2−2·8). At 2 years, event-free survival was 62.3% (95% CI, 51·1−71·7), progression-free survival 64·7% (95% CI, 53·5−73·8), duration of response 69·6% (95% CI, 57·2−79·0), and overall survival 86·9% (95% CI, 77·6−92·5). Most common AEs were asthenia (n=54, 61·4%), neutropenia (n=38, 43·2%), bronchitis (n=36, 40·9%), diarrhea (n=35, 39·8%), and muscle spasms (n=34, 38·6%). Neutropenia was the most common grade ≥3 toxicity; 4 (4·5%) patients had febrile neutropenia. Fifty-seven serious AEs were in 30/88 patients (34·1%); 18/88 (20·5%) deaths occurred (progressive lymphoma [n=10], infection [n=4], related cancer [n=1], and unknown cause [n=3]). No AEs were unanticipated. 6 Interpretations: Lenalidomide plus obinutuzumab is effective for patients with relapsed/refractory follicular lymphoma, including those with early relapse, with no increased toxicity compared with previous reports for lenalidomide plus rituximab. Funding: The Lymphoma Academic Research Organisation (LYSARC) sponsored the study, and Celgene and Roche provided investigator-initiated study grants