Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis
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Le résumé fourni par la source
Frontline therapy for transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) has advanced with anti-CD38 monoclonal antibody (mAb)-based regimens. Although quadruplet combinations incorporating daratumumab and isatuximab have demonstrated improved response rates and progression-free survival (PFS), comparative overall survival (OS) data remain limited. We performed a systematic review, network meta-analysis (NMA), and reconstructed individual patient data meta-analysis comparing survival outcomes of quadruplet versus triplet regimens in TI-NDMM. This study adhered to Cochrane and PRISMA guidelines and was registered prospectively (PROSPERO CRD420251033401). A comprehensive literature search through April 2025 identified randomized clinical trials (RCT) evaluating quadruplet and triplet regimens involving daratumumab, isatuximab, bortezomib, lenalidomide, and dexamethasone in any combination, compared to their backbone regimens, reporting OS and PFS. Four RCT (n = 2,038) were included. At 60 months, estimated PFS rates were: D-VRd (66.4%), I-VRd (63.2%), D-Rd (51.9%), and VRd (42.6%). Both D-VRd and I-VRd significantly improved PFS compared with D-Rd (HR 0.65; 95% CI 0.48-0.87; and HR 0.68; 95% CI 0.52-0.89) and VRd (HR 0.51; 95% CI 0.39-0.67; and HR 0.53; 95% CI 0.41-0.67). D-Rd also showed superior PFS over VRd (HR 0.77, 95% CI 0.64-0.93; P = 0.007). At 60 months, OS rates were: D-VRd (72.8%), I-VRd (72.2%), D-Rd (67.1%), and VRd (67.0%). Pooled analyses demonstrated that quadruplets significantly improved both PFS (64.7% vs. 46.3%; HR 0.57, 95% CI 0.47-0.69; P < 0.0001) and OS (72.5% vs. 67.1%; HR 0.78, 95% CI 0.63-0.96; P = 0.02) compared to triplet regimens. The OS benefit of quadruplets was consistent in comparisons against both D-Rd (HR 0.77; 95% CI: 0.60-0.98; P = 0.04) and VRd (HR 0.77; 95% CI: 0.62-0.97; P = 0.02). In the NMA, quadruplet regimens ranked highest for complete response, PFS, and OS. This meta-analysis supports anti-CD38 mAb-based quadruplet regimens as superior frontline therapy in TI-NDMM, significantly improving overall survival.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Survival impact of anti-CD38-based quadruplet regimens in transplant-ineligible newly diagnosed multiple myeloma: a network meta-analysis and reconstructed individual patient data meta-analysis
- Date Crossref
- 06/12/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Instituto Federal Fluminense pays non établi dans la noticeUniversité ou école supérieure
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Prefeitura Municipal de Campos dos Goytacazes pays non établi dans la noticeOrganisme public
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Universidade Estadual Paulista (Unesp) Hospital das Clínicas pays non établi dans la noticeUniversité ou école supérieure
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Universidade Federal da Bahia pays non établi dans la noticeUniversité ou école supérieure
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São Germano Oncologia pays non établi dans la noticeÉtablissement de santé
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Universidade Federal do Rio de Janeiro pays non établi dans la noticeUniversité ou école supérieure
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Faculdade de Medicina de Campos pays non établi dans la noticeInstitution
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Instituto Federal de Educação pays non établi dans la noticeStructure de recherche
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Rede D'Or Oncologia pays non établi dans la noticeInstitution
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Clínica São Germano pays non établi dans la noticeÉtablissement de santé
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Instituto Americas de Ensino pays non établi dans la noticeStructure de recherche
Instituto Federal Fluminense, Prefeitura Municipal de Campos dos Goytacazes et Hospital das Clínicas — Universidade Estadual Paulista (Unesp), avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.