DARATUMUMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: FINAL ANALYSIS OF TRANSPLANT-INELIGIBLE PATIENTS IN THE PHASE 3 CEPHEUS STUDY

@article{usmani2026daratumumab,
  title = {{DARATUMUMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: FINAL ANALYSIS OF TRANSPLANT-INELIGIBLE PATIENTS IN THE PHASE 3 CEPHEUS STUDY}},
  author = {Saad Z USMANI and Thierry FACON and Vania HUNGRIA and Nizar J BAHLIS and Christopher P VENNER and Marc BRAUNSTEIN and Ludek POUR and Josep MARTI and Supratik BASU and Yael C COHEN and Kenshi SUZUKI and Cyrille HULIN and Sebastian GROSICKI and Meral BEKSAC and Angelo MAIOLINO and Jaclyn STANZIOLA and Lorena LOPEZ-MASI and Matteo LOI and Melissa ROWE and Sonja ZWEEGMAN},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107857},
  url = {https://doi.org/10.1016/j.htct.2026.107857},
  note = {CC BY},
}

TY  - JOUR
TI  - DARATUMUMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: FINAL ANALYSIS OF TRANSPLANT-INELIGIBLE PATIENTS IN THE PHASE 3 CEPHEUS STUDY
AU  - Saad Z USMANI
AU  - Thierry FACON
AU  - Vania HUNGRIA
AU  - Nizar J BAHLIS
AU  - Christopher P VENNER
AU  - Marc BRAUNSTEIN
AU  - Ludek POUR
AU  - Josep MARTI
AU  - Supratik BASU
AU  - Yael C COHEN
AU  - Kenshi SUZUKI
AU  - Cyrille HULIN
AU  - Sebastian GROSICKI
AU  - Meral BEKSAC
AU  - Angelo MAIOLINO
AU  - Jaclyn STANZIOLA
AU  - Lorena LOPEZ-MASI
AU  - Matteo LOI
AU  - Melissa ROWE
AU  - Sonja ZWEEGMAN
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107857
UR  - https://doi.org/10.1016/j.htct.2026.107857
AB  - Background: The phase 3 CEPHEUS study established that daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) improved overall minimal residual disease (MRD)-negativity (neg) rates and progression-free survival (PFS) vs VRd in patients with transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM). The first analysis of the DVRd TIE subpopulation at a median follow-up of 58.7 months (mo) showed a complete response or better (≥CR) rate of 80.6% and overall MRD neg rate of 60.4%, with ∼70% of patients alive and progression free. Aims: This final analysis of the CEPHEUS TIE subpopulation describes a longer median follow-up of 76.0 mo. Methods: The primary endpoint of overall MRD neg rate (10-5 and ≥CR), and secondary endpoints, including investigator-assessed PFS and ≥CR rate, and sustained MRD neg (confirmed MRD neg ≥12 mo +/- 1 mo apart without MRD positivity in between and ≥CR) were assessed in the TIE population. The study was closed at the final analysis and patients were able to continue their study treatment via post-study access. Results: Of 395 patients enrolled, 289 patients with TIE NDMM received either DVRd (n=144) or VRd (n=145). The overall MRD neg rate at 10-5 was 61.1% for DVRd and 40.0% for VRd (odds ratio [OR] 2.35; 95% CI 1.47–3.77; P=0.0004) and at 10-6 was 46.5% for DVRd vs 27.6% for VRd (OR 2.27; 95% CI 1.39–3.71; P=0.0010). Sustained MRD neg rate at 10-5 was 49.3% for DVRd and 29.0% for VRd (OR 2.40; 95% CI 1.47–3.91; P=0.0005) and at 10-6 was 37.5% for DVRd and 16.6% for VRd (OR 3.01; 95% CI 1.73–5.24; P<0.0001). Overall ≥CR rate was 80.6% for DVRd and 61.4% for VRd (OR 2.64; 95% CI 1.54–4.51; P=0.0003). Median investigator-assessed PFS was not estimable (NE; 95% CI 74.81–NE) for DVRd and was 50.20 mo (95% CI 41.95–62.95) for VRd (hazard ratio [HR] 0.55; 95% CI 0.39–0.78; P=0.0007), with 59.3% for DVRd vs 38.3% for VRd alive and progression free at 72 mo. Overall survival favored DVRd over VRd (HR 0.84; 95% CI 0.57–1.24), particularly when censoring for COVID-19, which significantly impacted this study (HR 0.74; 95% CI 0.49–1.12). The treatment effect was consistent across most subgroups (Table). Conclusion: After median follow-up of over 6 years, the final analysis of the CEPHEUS trial demonstrated that TIE patients treated with DVRd continue to have deep and durable responses compared with those on VRd, which is crucial for patients for whom transplant is not an option. These data continue to reinforce DVRd as a standard of care in the TIE NDMM population.
SN  - 2531-1379
SN  - 2531-1387
ER  -