Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) usually have dismal prognostic outcomes. Venetoclax, a selective inhibitor of antiapoptotic protein B-cell lymphoma-2 (BCL-2), demonstrates antimyeloma activity in plasma cells with t(11;14) or high BCL-2 expression. OBJECTIVES: This meta-analysis aimed to investigate the efficacy and safety of venetoclax-based therapy in RRMM. DESIGN: This is a meta-analysis study. DATA SOURCES AND METHODS: PubMed, Embase, and Cochrane were searched for studies published up to 20 December 2021. Overall response rate (ORR), rate of very good partial response or better (≧VGPR), and complete response (CR) rate were pooled with the random-effects model. Safety was evaluated by the incidences of grade ≧3 adverse events. Subgroup analysis and meta-regression were performed to identify the causes of heterogeneities. All the analyses were conducted by STATA 15.0 software. RESULTS: A total of 14 studies with 713 patients were included for analysis. The pooled ORR, rate of ≧VGPR, and CR for all patients were 59% [95% confidence interval (CI) = 45–71%], 38% (95% CI = 26–51%), and 17% (95% CI = 10–26%), respectively. The median progression-free survival (PFS) ranged from 2.0 months to not reached (NR), and the median overall survival (OS) ranged from 12.0 months to NR. Meta-regression showed that patients treated with more drugs combined or less heavily pretreated had higher response rates. Patients with t(11;14) had superior ORR [relative risk (RR) = 1.47, 95% CI = 1.05–2.07], ≧VGPR (RR = 1.71, 95% CI = 1.12–2.60), CR (RR = 1.86, 95% CI = 1.34–2.57), PFS [hazard ratio (HR) = 0.47, 95% CI = 0.30–0.65], and OS (HR = 0.30, 95% CI = 0.08–0.52) compared with patients without t(11;14). Most grade ≧3 adverse events were hematologic, gastrointestinal, and infectious related and were manageable. CONCLUSION: Venetoclax-based therapy is an effective and safe option for RRMM patients, especially those with t(11;14).