A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy

Summary

The purpose of this study to determine if the addition of daratumumab to bortezomib + lenalidomide + dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity rate compared with VRd alone.

Timeline

Start

2018-11-06

Primary completion

2024-05-07

Completion

2026-04-21

Outcome

Met primary endpoint

registry analysis (superiority test); Arm A: Bortezomib-lenalidomide-dexamethasone (VRd) vs Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd); p =0.0004; Odds Ratio (OR) 2.07 (95% CI 1.38 to 3.10); Fisher Exact NCT03652064 ↗

registry analysis (superiority test); Arm A: Bortezomib-lenalidomide-dexamethasone (VRd) vs Arm B: Daratumumab-bortezomib-lenalidomide-dexamethasone (D-VRd); p <0.0001; Odds Ratio (OR) 2.37 (95% CI 1.58 to 3.55); Fisher Exact NCT03652064 ↗

Publications

• Zweegman S, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, Pour L, Marti J, Basu S, Cohen YC, Matsumoto M, Suzuki K, Hulin C, Legiec WM, Beksac M, Maiolino A, Takamatsu H, Perrot A, Turgut M, Liu W, Wang J, Van Brummelen E, Krevvata M, Lopez-Masi L, Carey J, Borgsten F, Rowe M, Carson R, Usmani SZ. Daratumumab in Transplant-Ineligible or -Deferred Newly Diagnosed Multiple Myeloma: Minimal Residual Disease in CEPHEUS. Blood Adv. 2026 Jun 3:bloodadvances.2026019937. doi: 10.1182/bloodadvances.2026019937. Online ahead of print.
• Usmani SZ, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, Pour L, Marti JM, Basu S, Cohen YC, Matsumoto M, Suzuki K, Hulin C, Grosicki S, Legiec W, Beksac M, Maiolino A, Takamatsu H, Perrot A, Turgut M, Ahmadi T, Liu W, Wang J, Chastain K, Vermeulen J, Krevvata M, Lopez-Masi L, Carey J, Rowe M, Carson R, Zweegman S. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025 Apr;31(4):1195-1202. doi: 10.1038/s41591-024-03485-7. Epub 2025 Feb 5.
• Abdallah N, Kumar SK. Up-Front Treatment of Elderly (Age >/=75 Years) and Frail Patients With Multiple Myeloma. J Natl Compr Canc Netw. 2024 Nov;22(9):e247039. doi: 10.6004/jnccn.2024.7039.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Daratumumab	Monoclonal antibody	1800 mg	Subcutaneous
Background	Bortezomib	Small molecule	1.3 mg/m2	Subcutaneous
Background	Dexamethasone	Small molecule	40 mg	Oral
Background	Lenalidomide	Other / unclassified	25 mg	Oral

Indications