First-Line treatment for transplant-ineligible newly diagnosed multiple myeloma: a Bayesian network meta-analysis of efficacy, safety, and high-risk subgroups
In brief
D-VRd ranks highest for progression-free survival in transplant-ineligible newly diagnosed myeloma
In a Bayesian network meta-analysis of six trials (3,162 patients), all four anti-CD38 regimens beat lenalidomide-dexamethasone, with daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd) achieving the top PFS ranking. Overall survival favored a dexamethasone-sparing schedule, but mature OS data are lacking, and safety profiles differ, especially higher neutropenia rates with anti-CD38 combos.
- Journal
- Frontiers in immunology (Q1)
- Published
- 24 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Dani Zhong, Hao Cheng, Lin Zeng, Chun Tian, Chunchun Liang, Hongyu Wei, et al.
- PMID
- 42707226
- DOI
- 10.3389/fimmu.2026.1869797
Why clinicians should know about it
- Picked for Hematology (top studies of the week, 13 September 2026): Network meta‑analysis of first‑line regimens for transplant‑ineligible NDMM
- Picked for Pharmacology (medical) (top studies of the week, 13 September 2026): Ranked by evidence level and journal quartile
Abstract
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 IFM2017-03 schedule (D-R-limited dexamethasone) separate from continuous D-Rd. All four anti-CD38-containing regimens improved progression-free survival (PFS) relative to lenalidomide-dexamethasone, with D-VRd ranking highest (SUCRA 81.5%). For overall survival (OS), D-R-limited 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-lenalidomide regimens retained a progression-free survival benefit relative to lenalidomide-dexamethasone. Regarding safety, several anti-CD38-containing regimens increased grade ≥3 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.