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Immunol."],"abstract":"<jats:p>Anti-CD38 monoclonal antibody-based regimens have emerged as the first-line standard of care for transplant-ineligible newly diagnosed multiple myeloma (NDMM), yet direct head-to-head comparisons between individual regimens remain limited. The systematic review identified 11 eligible randomised controlled trials; 6 of these, involving 3162 patients, entered the Bayesian network meta-analysis to systematically evaluate the efficacy, safety, and benefits in the cytogenetically high-risk subgroup across 7 treatment nodes, keeping the dexamethasone-sparing IFM2017\u201303 schedule (D-R\u2013limited dexamethasone) separate from continuous D-Rd. All four anti-CD38-containing regimens improved progression-free survival (PFS) relative to lenalidomide\u2013dexamethasone, with D-VRd ranking highest (SUCRA 81.5%). For overall survival (OS), D-R\u2013limited dexamethasone ranked highest (SUCRA 87.4%), but OS follow-up is considerably less mature for the quadruplet trials, and no pairwise comparison among the anti-CD38-containing regimens reached significance for either outcome. High-risk subgroup estimates could not rank regimens against one another, but both daratumumab\u2013lenalidomide regimens retained a progression-free survival benefit relative to lenalidomide\u2013dexamethasone. Regarding safety, several anti-CD38-containing regimens increased grade \u22653 neutropenia, whereas infection signals were regimen- and endpoint-specific. This study provides comprehensive evidence to inform individualized first-line treatment decisions for transplant-ineligible NDMM patients.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1869797","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:31:11Z","timestamp":1787549471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["First-Line treatment for transplant-ineligible newly diagnosed multiple myeloma: a Bayesian network meta-analysis of efficacy, safety, and high-risk subgroups"],"prefix":"10.3389","volume":"17","author":[{"given":"Dani","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Hematology\/Oncology, Guangxi Medical University Cancer Hospital","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, 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