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SYSTEMATIC REVIEW article

Front. Oncol.

Sec. Hematologic Malignancies

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1619115

Addition of daratumumab to standard triplet regimens achieved better survival in newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials

Provisionally accepted
Bin  HuBin HuJun  WangJun WangDan  FangDan FangLing  JiangLing JiangTianqi  LiTianqi LiJinxia  CaoJinxia Cao*
  • The First People's Hospital of Changde City, Changde, China

The final, formatted version of the article will be published soon.

Background: Triplet regimens, such as bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-melphalan-prednisone (VMP), were standard treatments for newly diagnosed multiple myeloma (NDMM), but they were non-curative for most patients. The incorporation of daratumumab into these regimens, resulting in quadruplet therapies, has shown improved outcomes, though concerns over increased toxicity remain. Methods: In this systematic review and meta-analysis, we aimed to compare the efficacy and safety of daratumumab-incorporated quadruplet regimens versus traditional triplet regimens in NDMM. A search of PubMed, EMBASE, and the Cochrane Library identified six randomized controlled trials (RCTs) with 3,056 patients. Outcomes included response rates, minimal residual disease (MRD) negativity rate, progression-free survival (PFS), and adverse events. Results: Compared with triplet regimens, daratumumab-incorporated quadruplet combinations achieved a higher overall survival rate (ORR) (pooled OR = 2.36, 95% CI: 1.56-3.56, P < 0.0001), rate of complete response (CR) or better (pooled OR = 2.35, 95% CI: 1.99-2.77, P < 0.0001), very good partial response (VGPR) or better (pooled OR = 2.58, 95% CI: 1.76-3.79, P < 0.0001) and MRD negativity (pooled OR = 3.55, 95% CI: 2.54-4.96, P < 0.0001). The addition of daratumumab to triplet regimens significantly improved PFS compared with triplet regimens (pooled HR = 0.45, 95% CI: 0.39–0.52, P < 0.0001). Regarding safety, quadruplet regimens were associated with a higher incidence of lymphopenia, upper respiratory tract infection, pyrexia, and pneumonia. Conclusion: Incorporating daratumumab into backbone triplet regimens is associated with improved response rates, deeper remission and prolonged PFS with acceptable toxicity profile in patients with NDMM. The trial was registered at https://inplasy.com as INPLASY2024120026.

Keywords: Daratumumab, quadruplet regimens, triplet regimens, Multiple Myeloma, Meta-analysis

Received: 27 Apr 2025; Accepted: 16 Oct 2025.

Copyright: © 2025 Hu, Wang, Fang, Jiang, Li and Cao. 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: Jinxia Cao, valentina8805@163.com

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