Triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma: A meta-analysis of phase III randomized controlled trials

During the past decades, several prospective trials had been conducted to assess the efficacy and toxicities of triplet versus doublet combination regimens for the treatment of relapsed or refractory multiple myeloma (RRMM), but the results were controversial. We thus performed a systematic literature search to identify relevant trials. Summary hazard ratios (HRs), relative risks (RRs), and 95% confidence intervals (95%CIs) were calculated. A total of 3197 RRMM patients were included for analysis. The pooled results demonstrated that triplet combination therapies significantly improve OS (HR 0.83, 95%CI: 0.71-0.94, p = 0.004) and PFS (HR 0.68, 95%CI: 0.62-0.74, p < 0.001). The pooled RRs of ORR, very good partial response (VGPR) and complete response (CR) with triplets vs. doublets were 1.19 (95%CI: 1.10-1.27), 1.44 (95%CI: 1.18-1.77), and 1.76 (95%CI: 1.04-2.97), respectively, indicating that the RRs of achieving deeper responses were higher with triplets, though the RRs of overall ≥ grade 3 adverse events (RR 1.11, p = 0.001) and ≥grade 3 thrombocytopenia (RR 1.64, p = 0.009) was higher with triplets. In conclusion, our meta-analysis demonstrated that triplet regimens result in improved OS, PFS, ORR, VGPR, and CR when compared to doublets, though the risk of grade 3 and 4 adverse events were higher with triplets.