{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:23:34Z","timestamp":1780377814342,"version":"3.54.1"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFA1103501"],"award-info":[{"award-number":["2022YFA1103501"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u2265 3 adverse events. Results: In NDMM patients, isatuximab significantly improved PFS (HR = 0.66, 95% CI: 0.52\u20130.84, p = 0.001) and MRD negativity rates (RR = 1.28, 95% CI: 1.13\u20131.45, p &lt; 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\u20130.74, p &lt; 0.001) and showed strong trends favoring OS (HR = 0.81, 95% CI: 0.65\u20131.00, p = 0.051) and ORR (RR = 1.30, 95% CI: 0.79\u20132.16, p = 0.303), while significantly increasing MRD negativity (RR = 4.37, 95% CI: 0.60\u201331.68, 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 \u2265 3 adverse events RRMM (RR = 1.18, p &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers17213494","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T03:33:07Z","timestamp":1761881587000},"page":"3494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Isatuximab Combination Therapy in Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7365-9214","authenticated-orcid":false,"given":"Chi","family":"Wang","sequence":"first","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Xu","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Jiang","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhe","family":"Chen","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-5945","authenticated-orcid":false,"given":"Yu","family":"Lan","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1002\/ajh.27422","article-title":"Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management","volume":"99","author":"Rajkumar","year":"2024","journal-title":"Am. 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