Anti-CD38-based quadruplet versus triplet induction regimens in transplant-ineligible newly diagnosed multiple...

This systematic review and meta-analysis compared the efficacy and safety of anti-CD38-containing quadruplet and triplet regimens in transplant-ineligible patients with newly diagnosed multiple myeloma (TIE-NDMM).

A comprehensive literature search was conducted across PubMed, Embase, and Cochrane databases up to April 30, 2025. Randomized controlled trials (RCTs) comparing anti-CD38-based quadruplet and triplet regimens were analysed for outcomes including efficacy and toxicity.

Six RCTs with 2089 patients were included. Quadruplet regimens yielded significantly greater PFS (HR 0.49, 95% CI: 0.39-0.61; P < 0.00001, I² = 56%) and OS (HR 0.64, 95% CI: 0.44-0.93; P = 0.02, I² = 70%) than triplet regimens. The addition of anti-CD38 increased the rates of MRD negativity (RR 1.95, 95% CI: 1.32-2.89, P = 0.0008, I² = 89%) and sustained MRD negativity at ≥ 12 months (RR 2.70, 95% CI: 1.54-4/75, P = 0.0005, I² = 80%), despite a slight increase in severe adverse events (RR 1.16, 95% CI: 1.05-1.30, P = 0.006, I² = 17%) and grade 3/4 infections (RR 1.36, 95% CI: 1.14-1.6, P = 0.0004, I² = 0%).

Anti-CD38-based quadruplet regimens are superior to triplet regimens for non-frail TIE-NDMM patients, improving key efficacy outcomes with manageable safety concerns.