Efficacy and Safety of Isatuximab Combination Therapy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled
Chi Wang1, Zhengyang Xu1, Meilin Jiang1
1State Key Laboratory of Experimental Hematology, Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, China.
Background:
This meta-analysis evaluates the efficacy and safety of isatuximab, an anti-CD38 monoclonal antibody, in combination regimens for newly diagnosed (NDMM) and relapsed/refractory multiple myeloma (RRMM).
Methods:
We systematically searched major databases for randomized controlled trials (RCTs) comparing isatuximab-based therapy with standard regimens up to September 2025. Efficacy and safety analyses were performed separately for NDMM and RRMM populations using random-effects models. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), very good partial response (VGPR) or better, and minimal residual disease (MRD) negativity rate. Safety was assessed by grade ≥ 3 adverse events.
Results:
In NDMM patients, isatuximab significantly improved PFS (HR = 0.66, 95% CI: 0.52-0.84, p = 0.001) and MRD negativity rates (RR = 1.28, 95% CI: 1.13-1.45, p < 0.001), but not OS (HR = 1.01, p = 0.937), ORR (RR = 1.02, p = 0.49), or VGPR or better (RR = 1.10, p = 0.13). In RRMM patients, isatuximab significantly improved PFS (HR = 0.61, 95% CI: 0.50-0.74, p < 0.001) and showed strong trends favoring OS (HR = 0.81, 95% CI: 0.65-1.00, p = 0.051) and ORR (RR = 1.30, 95% CI: 0.79-2.16, p = 0.303), while significantly increasing MRD negativity (RR = 4.37, 95% CI: 0.60-31.68, p = 0.144). A trend toward improved OS was observed in RRMM (HR = 0.81, p = 0.051). In NDMM, PFS benefit was significant for standard-risk but not high-risk cytogenetics. Safety analysis showed an increased risk of grade ≥ 3 adverse events RRMM (RR = 1.18, p < 0.001) but not in NDMM (RR = 1.08, p = 0.064), primarily driven by neutropenia (NDMM RR = 1.96, p = 0.003; RRMM RR = 1.77, p = 0.039) and pneumonia in NDMM (RR = 1.80, p = 0.001).
Conclusion:
Isatuximab-based regimens significantly improve PFS and depth of response with a manageable safety profile, supporting its use across MM settings, though efficacy in NDMM may vary by cytogenetic risk.
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