Comparative safety and efficacy of venetoclax-combination therapies versus obinutuzumab-combination therapies in chronic lymphocytic leukemia: A systematic review and meta-analysis.

Abstract

e19028 Background: Chronic lymphocytic leukemia (CLL) treatment has changed substantially with targeted therapies that achieve superior outcomes compared with traditional chemoimmunotherapy. Venetoclax, a BCL-2 inhibitor that promotes apoptosis, and obinutuzumab, a type II anti-CD20 monoclonal antibody that induces direct cell death and enhances antibody-dependent cellular cytotoxicity, are increasingly used in CLL patients and are generally well-tolerated. However, comparative evidence on their effectiveness remains limited. We conducted a systematic review and meta-analysis of randomized controlled trials to assess efficacy and safety. This analysis addresses existing evidence gaps and aims to support more informed clinical decision-making in CLL management. Methods: A systematic literature search (2010–2026) was conducted using the MeSH terms “BCL2 Inhibitors,” “type II anti-CD20 monoclonal antibody,” “Obinutuzumab,” “Venetoclax,” and “CLL.” Screening across PubMed (412), Google Scholar (1,236), and the Cochrane Library (128) identified 1,776 records. After duplicate removal and screening, six randomized controlled trials were included, while editorials, reviews, case reports, and guidelines were excluded. Eligible studies comprised RCTs and observational studies comparing venetoclax-based versus obinutuzumab-based regimens. Pooled effect sizes were estimated using random-effects models, with heterogeneity assessed via the I² statistic. Risk of bias for RCTs was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and the review was conducted in accordance with updated PRISMA guidelines. Results: Six randomized controlled trials comprising 2,184 patients were included in this systematic review and meta-analysis. The primary outcomes were progression-free survival (PFS), undetectable minimal residual disease (uMRD), and mortality. Venetoclax-based regimens demonstrated significantly improved PFS compared with obinutuzumab-based therapies (RR = 1.95; 95% CI, 1.16–3.27; p = 0.01). The pooled analysis showed a higher uMRD rate in the venetoclax arm, but the difference was not statistically significant (RR = 1.63; 95% CI, 0.91–2.90; p = 0.10). Venetoclax-based therapies were associated with reduced mortality (RR = 0.71; 95% CI, 0.59–0.85; p = 0.0003) with no heterogeneity (I² = 0%). Secondary outcomes, including grade 3–4 adverse events (RR = 1.07; 95% CI, 0.94–1.23; p = 0.30) and neutropenia (RR = 0.92; 95% CI, 0.78–1.08; p = 0.31), showed no significant differences between the groups. Conclusions: Venetoclax-based therapies improved progression-free survival and reduced mortality compared with obinutuzumab, providing clinically relevant evidence to guide CLL treatment decisions, though larger studies are needed to confirm these findings.