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.
背景：本荟萃分析评估了抗CD38单克隆抗体伊沙妥昔单抗联合方案在新诊断多发性骨髓瘤（NDMM）和复发/难治性多发性骨髓瘤（RRMM）患者中的疗效与安全性。方法：我们系统检索了截至2025年9月比较伊沙妥昔单抗为基础的治疗方案与标准方案的随机对照试验（RCTs）。采用随机效应模型分别对NDMM和RRMM人群进行疗效与安全性分析。疗效指标包括无进展生存期（PFS）、总生存期（OS）、总体缓解率（ORR）、非常好的部分缓解（VGPR）或更佳缓解率，以及微小残留病（MRD）阴性率。安全性通过≥3级不良事件进行评估。结果：在NDMM患者中，伊沙妥昔单抗显著改善PFS（HR = 0.66，95% CI：0.52–0.84，p = 0.001）和MRD阴性率（RR = 1.28，95% CI：1.13–1.45，p < 0.001），但未显著改善OS（HR = 1.01，p = 0.937）、ORR（RR = 1.02，p = 0.49）或VGPR及以上缓解率（RR = 1.10，p = 0.13）。在RRMM患者中，伊沙妥昔单抗显著改善PFS（HR = 0.61，95% CI：0.50–0.74，p < 0.001），并在OS（HR = 0.81，95% CI：0.65–1.00，p = 0.051）和ORR（RR = 1.30，95% CI：0.79–2.16，p = 0.303）方面显示出有利趋势，同时显著提高MRD阴性率（RR = 4.37，95% CI：0.60–31.68，p = 0.144）。RRMM患者中观察到OS改善趋势（HR = 0.81，p = 0.051）。在NDMM患者中，PFS获益在标准风险细胞遗传学患者中显著，但在高风险患者中不显著。安全性分析显示，RRMM患者≥3级不良事件风险增加（RR = 1.18，p < 0.001），而NDMM患者未显著增加（RR = 1.08，p = 0.064），风险增加主要源于中性粒细胞减少症（NDMM RR = 1.96，p = 0.003；RRMM RR = 1.77，p = 0.039）和NDMM患者的肺炎（RR = 1.80，p = 0.001）。结论：基于伊沙妥昔单抗的方案能显著改善PFS和缓解深度，且安全性可控，支持其在多发性骨髓瘤各阶段的应用，尽管其在NDMM中的疗效可能因细胞遗传学风险而异。
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