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

• For patients with untreated high tumor burden follicular lymphoma, obinutuzumab and lenalidomide resulted in a 2-year PFS rate of 93.3%

• Obinutuzumab combined with lenalidomide was well tolerated with the most common adverse events being diarrhea, rash, and fatigue

Follicular lymphoma (FL) has a clinical course often defined 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, with debate remaining as to what is the preferred approach. Given prior benefits seen in 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 (ADCC). Eligibility criteria included a diagnosis of FL, grade 1-3a, stage II-IV, ECOG ≤ 2, adequate organ function, and high tumor burden according to Groupe d'Étude des Lymphomes Folliculaires (GELF) criteria. Participants received six cycles of induction with the combination, followed by 24 cycles of maintenance. Among 90 patients, the primary endpoint, 2-year PFS, was 93.3% (95% confidence interval (CI), 88.2-98.6%), and median progression-free survival (PFS) was not reached with a median follow up of 70.7 months. The complete response rate (CRR) 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 ³ 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 resulted in robust and durable responses with favorable 2-year PFS and manageable safety profile. This study was registered at clinicaltrials.gov (NCT02871219)