Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS
In brief
Daratumumab combination cuts progression or death risk by 49% in transplant-ineligible myeloma
In 289 transplant-ineligible patients with newly diagnosed multiple myeloma, adding daratumumab to bortezomib, lenalidomide, and dexamethasone raised minimal residual disease negativity from 39% to 60% after a median 58.7 months. The combination also lowered the risk of progression or death by 49%; overall survival favored the regimen, but follow-up is not yet mature.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 25 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Saad Z Usmani, Thierry Facon, Vania Hungria, Nizar J Bahlis, Christopher P Venner, Marc Braunstein, et al.
- PMID
- 42789828
- DOI
- 10.1200/JCO-26-00401
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 27 September 2026): Phase III DVRd vs VRd improves MRD & PFS
Abstract
The phase III CEPHEUS trial (ClinicalTrials.gov identifier: NCT03652064) of patients with transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM; N = 395) demonstrated improved overall minimal residual disease (MRD) negativity rates among patients achieving ≥complete response and progression-free survival (PFS) with daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd. We present efficacy and safety outcomes in the CEPHEUS TIE subgroup (N = 289; DVRd, n = 144; VRd, n = 145). Patients were either age 18-70 years with ≥1 comorbidity likely to negatively affect tolerability of high-dose chemotherapy with autologous stem cell transplantation or age ≥70 years. At a median follow-up of 58.7 months, the MRD negativity rate (10-5) was 60.4% (DVRd) versus 39.3% (VRd; P = .0004). Rates of sustained MRD negativity (10-5) for ≥12 months (47.2% v 28.3%; P = .0010) and ≥24 months (40.3% v 22.8%; P = .0015) were significantly higher with DVRd. Risk of disease progression or death was 49% lower for DVRd versus VRd (hazard ratio [HR], 0.51 [95% CI, 0.35 to 0.74]; P = .0003). Although immature, overall survival favored DVRd (HR, 0.66 [95% CI, 0.42 to 1.03]). Adverse events were consistent with known safety profiles. This analysis demonstrates that the deep responses achieved with DVRd translate into improved PFS in patients with TIE NDMM, reinforcing DVRd as a standard of care.
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.