Comparative safety and efficacy of obinutuzumab versus rituximab in combination with chemotherapy for follicular lymphoma: A systematic review and meta-analysis.

Abstract

7068 Background: Follicular lymphoma is one of the most common non-Hodgkin lymphoma subtypes, typically presenting with advanced-stage disease and a relapsing-remitting course. Over the past two decades, anti-CD20 monoclonal antibodies combined with chemotherapy have significantly improved outcomes. Rituximab, a first-generation anti-CD20 antibody, has been the standard of care since approval. Obinutuzumab, a type II glycoengineered anti-CD20 antibody with enhanced antibody-dependent cellular cytotoxicity and direct cell death mechanisms, is a newer option with potential efficacy advantages. While individual randomized trials have shown promising results with obinutuzumab, comparative data on safety and efficacy remain limited. Methods: A systematic search of PubMed, ClinicalTrials.gov, Scopus, Embase, and Cochrane CENTRAL identified relevant English-language randomized controlled trials and observational studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models based on heterogeneity. Statistical significance was set at p<0.05, and heterogeneity was assessed using the I² statistic. Analyses were performed using Review Manager version 5.3, following PRISMA guidelines. Results: Three studies met inclusion criteria, including two retrospective observational studies (Claustre et al., 2023; Berger et al., 2023) and one randomized controlled trial (Marcus et al., 2017). The pooled sample included 1,482 patients, of whom 53% were female. Compared with rituximab, obinutuzumab was associated with higher partial response rates (OR=0.66; 95% CI: 0.50–0.89; p=0.006) and improved disease progression outcomes (OR=0.64; 95% CI: 0.49–0.86; p=0.002). No significant differences were observed in overall response rate (OR=1.18; 95% CI: 0.84–1.65; p=0.34) or complete response (OR=0.82; 95% CI: 0.63–1.06; p=0.13). Obinutuzumab was associated with a higher incidence of adverse events during induction (OR=1.56; 95% CI: 1.04–2.33; p=0.03) and maintenance (OR=1.48; 95% CI: 1.13–1.93; p=0.004). Treatment discontinuation, dose reduction, or interruption due to adverse events occurred more frequently with obinutuzumab (OR=1.65; 95% CI: 1.13–2.42; p=0.01), as did neutropenia (OR=1.38; 95% CI: 1.12–1.71; p=0.002). Conclusions: This meta-analysis demonstrates that obinutuzumab provides improved efficacy, including higher partial response rates and reduced disease progression, compared with rituximab in follicular lymphoma. However, this benefit is accompanied by increased toxicity. Treatment selection should balance efficacy gains against safety risks.