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December 8, 2025BloodOpen Access

Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) – interim results from the randomized Phase III COBRA trial.

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Authors

DDDominik DytfeldTKTadeusz KubickiMRMarcin Rymko

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Overview

Randomized trial shows KRd improves MRD-negative CR and PFS in newly diagnosed multiple myeloma, suggesting enhanced treatment efficacy over VRd.

Key Points

  • To evaluate the efficacy and safety of KRd versus VRd in patients with newly diagnosed multiple myeloma.
  • Patients with NDMM were randomized to receive either KRd or VRd.
  • KRd consisted of carfilzomib, lenalidomide, and dexamethasone; VRd included bortezomib, lenalidomide, and dexamethasone.
  • Minimal residual disease and progression-free survival were the co-primary endpoints, assessed after 12 months.
  • KRd showed higher MRD-negative complete response rates at both 10⁻⁵ and 10⁻⁶ thresholds compared to VRd.
  • KRd treatment resulted in longer progression-free survival compared to VRd with HR = 0.57.
  • Overall response rates were similar between KRd and VRd, but KRd had a higher complete response rate (71% vs 53%).

Cite This Study

Dytfeld et al. (2025) studied this question.

synapsesocial.com/papers/693624d44fa91c937236cff2https://doi.org/10.1182/blood-2025-99
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Cytogenetic subgroup analysis of the advance trial: A randomized multi-center study of carfilzomib, lenalidomide and dexamethasone (KRd) with or without daratumumab (D) in patients with newly diagnosed multiple myeloma (NDMM)2025
  2. 2Real-world experience with first-line regimens in transplant-ineligible patients with multiple myeloma2025
  3. 3Double hit ultra-high risk myeloma treated with isatuximab, bortezomib, lenalidomide, dexamethasone and cyclophosphamide (Isa-VRDc) induction and isa-VRD consolidation: Initial results of the UK myeloma research alliance (UKMRA)  RADAR trial in newly diagnosed transplant eligible patients2025
  4. 4Early rescue intervention with daratumumab, pomalidomide and dexamethasone (DPd) in high-risk smoldering myeloma (HR-SMM) patients included in the GEM-CESAR treated with carfilzomib, lenalidomide and dexamethasone (KRd)- autologous stem cell transplantation (ASCT)-krd-rd2025 · 2 citations
  5. 5Updated results from the frailty-stratified, randomised controlled bayesian adaptive trial of bortezomib versus lenalidomide in transplant ineligible myeloma (TI NDMM) – the FRAIL-m study (AMaRC 19-01; ALLG MM22)2025