Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS

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.

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Journal
Journal of Clinical Oncology
Published
2026-09-25
DOI
https://doi.org/10.1200/jco-26-00401
Primary Topic
Multiple Myeloma Research and Treatments
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article
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article

Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS

Saad Z. Usmani, Marc Justin Braunstein, Luděk Pour, Ângelo Maiolino et al.
Journal of Clinical Oncology
Multiple Myeloma Research and Treatments
article

Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS

Saad Z. Usmani, Marc Justin Braunstein, Luděk Pour, Ângelo Maiolino, Thierry T.F. Facon, Hiroyuki Takamatsu, Robin L. Carson, Sebastian Grosicki, Nizar Jacques Bahlis, Emilie M.J. van Brummelen, Yael Chava Cohen, Meral Beksaç, Aurore Perrot, Sonja Zweegman, Maria Krevvata, Wojciech Maciej Legiec, Supratik Basu, Jaclyn Stanziola, Mehmet Turgut, Josep Maria Martí, Vania Tietsche de Moraes Hungria, Lorena Lopez-Masi, Matteo Loi, Melissa Rowe, Kenshi Suzuki, Morio Matsumoto, Cyrille Hulin, Weiping Liu, Jianping Wang, Christopher P. Venner
article en

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.

Journal of Clinical Oncology
University of Wolverhampton (GB), Universidade Federal do Rio de Janeiro (BR), Johnson & Johnson (United States) (US), Memorial Sloan Kettering Cancer Center (US), Université Toulouse III - Paul Sabatier (FR), University of British Columbia (CA), University of Alberta (CA), Tel Aviv University (IL), Medical University of Silesia (PL), University of Calgary (CA), Université Fédérale de Toulouse Midi-Pyrénées (FR), Ondokuz Mayıs University (TR), Université de Lille (FR), Tel Aviv Sourasky Medical Center (IL), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Toulouse (FR), NYU Langone Health (US), Institute of Cancer Research (CA), University Hospital Mútua de Terrassa (ES), University Hospital Brno (CZ), Japanese Red Cross Medical Center (JP), Kanazawa University Hospital (JP), São Germano Oncologia (BR), Hôpital Cardiologique du Haut-Lévêque (FR), Istinye University (TR), Lublin Oncology Center (PL), Johnson Electric (China) (CN), National Hospital Organization (JP), Johnson & Johnson (United Kingdom) (GB), Liv Hospital (TR), The Royal Wolverhampton NHS Trust (GB), Johnson & Johnson (Netherlands) (NL), Cross Cancer Institute (CA), Université de Toulouse (FR), Vrije Universiteit Amsterdam (NL)
Good health and well-being
Openalex Percentile: Top 11%
Multiple Myeloma Research and Treatments
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