Obinutuzumab Maintenance in Follicular Lymphoma Is Associated With Better Progression Free Survival and Comparable Toxicity

Background The GALLIUM trial showed improved progression‐free survival (PFS) with obinutuzumab (O)‐based chemoimmunotherapy in first‐line treatment of follicular lymphoma (FL), although with increased toxicity compared to rituximab (R). Our previous real‐world study found similar toxicity between these protocols during induction. Aim To compare real‐world toxicity and outcomes of R versus O maintenance therapy in FL patients following first‐line chemoimmunotherapy. Methods A multicenter retrospective study included FL patients treated with first‐line R‐ or O‐based chemoimmunotherapy. The primary outcome was any infection up to 6 months post‐maintenance. Secondary outcomes included other toxicities, PFS, and overall survival (OS). Results We analyzed 134 patients (R: 71, O: 63). Baseline characteristics were similar except for higher diabetes and hypertension rates in the R group. The median number of maintenance cycles was comparable. Infections occurred in 56% of patients, with no significant difference (50.7% R vs. 61.9% O, p = 0.21). Grade 3 infections, febrile neutropenia, and treatment discontinuation rates were comparable between groups. Pneumonia and viral infections were less frequent with R versus O (13.8% vs. 28.1%, p = 0.019 and 19% vs. 39%, p = 0.004, respectively), while infusion reactions were higher (8.4% vs. 0%, p = 0.028). After 5.5 years, PFS favored O (19.7% vs. 4.8%, p = 0.028), with similar OS. Conclusions In real‐world settings, rituximab‐ and obinutuzumab‐based chemoimmunotherapy with maintenance for FL exhibited a similar toxicity profile, with differences in specific infections. Obinutuzumab had superior PFS and similar OS compared with rituximab therapy, supporting obinutuzumab usage in first‐line chemoimmunotherapy, especially in selected young and fit patients.