SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Cluster of Differentiation 38 Monoclonal Antibody Therapy in the Treatment of Multiple Myeloma: A Systematic Review and Meta-Analysis
Provisionally accepted
- The Second Affiliated Hospital of the Shandong First Medical University, The Second Affiliated Hospital of the Shandong First Medical University, China
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Background: Cluster of Differentiation 38 (CD38) monoclonal antibodies, including daratumumab and isatuximab, have demonstrated clinical activity in relapsed or refractory multiple myeloma. This study aims to systematically evaluate the efficacy and safety of CD38-targeted monoclonal antibodies compared with standard regimens. Methods: This study searched PubMed, the Cochrane Library, Web of Science, and Embase through June 30, 2025, for randomized controlled trials comparing CD38 antibodies (alone or in combination) with proteasome inhibitor– or immunomodulatory agent–based control regimens in adults with multiple myeloma. Two reviewers independently screened studies, extracted data, and assessed risk of bias (Cochrane Risk of Bias 2.0). Pooled risk ratios (RRs) and hazard ratios (HRs) were estimated using fixed-or random-effects models according to I² heterogeneity. Publication bias was examined by Egger's test. Results: A total of eight randomized controlled trials (RCTs) with 2,821 patients were included. The pooled overall response rate (ORR) was significantly improved with CD38-targeted therapies (relative risk [RR] 1.59; 95% confidence interval [CI] 1.32–1.92; P < 0.001). PFS was also significantly prolonged (hazard ratio [HR] 0.50; 95% CI 0.39–0.61; P < 0.001). Subgroup analyses indicated consistent benefits across renal function, age groups, and prior therapy lines. However, CD38-targeted therapies were associated with higher rates of non-hematologic adverse events, including infections and diarrhea. Conclusions: CD38 monoclonal antibodies enhance depth of response and prolong progression-free survival in multiple myeloma, with an acceptable safety profile, supporting their integration into treatment algorithms.
Keywords: CD38 monoclonal antibody, Cluster of differentiation 38, Daratumumab, isatuximab, Meta-analysis, Multiple Myeloma
Received: 18 Aug 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Liu, Lv and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiao-Fen Zhang
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