SynthesisFrontiers in immunology2025
The addition of CD38 monoclonal antibody to triplet regimens improves survival in newly diagnosed multiple myeloma with high-risk cytogenetics: a systematic review and meta-analysis of randomized controlled trials.
Synthesis in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: The efficacy of CD38 monoclonal antibody (mAb)-based quadruplet regimens versus triplet regimens in newly diagnosed multiple myeloma (NDMM) patients with high-risk cytogenetics remains controversial. This meta-analysis aims to consolidate evidence from randomized controlled trials (RCTs) to resolve this clinical uncertainty. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library for RCTs comparing CD38 mAb-based quadruplet regimens with triplet regimens in NDMM patients with high-risk cytogenetics. The primary outcomes were the rate of minimal residual disease (MRD) negativity at a sensitivity of 10 Results: Nine RCTs comprising 4557 patients were included. Compared to triplet regimens, CD38 mAb-based quadruplet regimens were associated with a significantly higher rate of MRD negativity (pooled OR = 2.02, 95% CI: 1.41-2.88, P = 0.0001) and a significantly improved PFS (pooled HR = 0.74, 95% CI: 0.59-0.94, P = 0.01). However, subgroup analyses revealed that the PFS benefit was not significant for isatuximab-based quadruplet regimens (pooled HR = 1.04, 95% CI: 0.67-1.62, P = 0.84) or in transplant-ineligible patients (pooled HR = 0.79, 95% CI: 0.56-1.13, P = 0.19). Conclusion: The incorporation of CD38 mAbs, particularly daratumumab, into triplet regimens improves depth of response and PFS in NDMM patients with high-risk cytogenetics. Systematic review registration: https://inplasy.com/inplasy-2025-10-0103/ , identifier INPLASY2025100103.
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