A Phase 2 Study of Obinutuzumab Combined with Lenalidomide in Previously Untreated High Tumor Burden Follicular Lymphoma.

ABSTRACT:Follicular lymphoma (FL) has a clinical course that is often characterized by high response rates to first-line therapy, followed by multiple relapses over a prolonged natural history. Currently, there are multiple possible approaches to frontline therapy for untreated advanced-stage FL, but there is an ongoing debate around what is the preferred approach. Based on the benefits seen with combining lenalidomide, an immunomodulatory agent, with rituximab, an anti-CD20 antibody, we aimed to evaluate the safety and efficacy of lenalidomide in combination with obinuzutumab, an anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity. The eligibility criteria included a diagnosis of FL, grade 1 to 3a, stage II to IV, Eastern Cooperative Oncology Group performance status ≤ 2, adequate organ function, and high tumor burden according to the Groupe d'Étude des Lymphomes Folliculaires criteria. Participants received 6 cycles of induction with the combination, followed by 24 cycles of maintenance. Among 90 patients, the primary end point, 2-year progression-free survival (PFS), was 93.3% (95% confidence interval [CI], 88.2-98.6), and the median PFS was not reached with a median follow-up of 70.7 months. The complete response rate at 30 months was 89.7% (95% CI, 81.3-95.2). The most common adverse events (AEs) of any grade were diarrhea (61.1%), maculopapular rash (53.3%), and fatigue (52.2%). The most common AEs ≥ grade 3 were neutropenia (18.9%), maculopapular rash (11.1%), and pneumonia (6.7%). In this single-center trial, these findings indicate that, for patients with previously untreated, high tumor burden FL, obinutuzumab and lenalidomide led to robust and durable responses with a favorable 2-year PFS and manageable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT02871219.