A study presented by Saad Usmani, MD, MBA, of the Memorial Sloan Kettering Cancer Center, as part of the SOHO 2025 Annual Meeting, showed that the combination of daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRd) improved outcomes in newly diagnosed, transplant-ineligible patients with multiple myeloma (MM), regardless of cytogenetic risk.
An analysis of the phase 3 CEPHEUS study compared outcomes for D-VRd versus VRd alone based on cytogenetic risk subgroups.
Among the 395 patients (D-VRd, n=197; VRd, n=198) included, 298 had standard-risk (SR) disease, 52 had high-risk disease [including del(17p), t(4;14), and/or t(14;16)], 184 had revised (R)-SR disease, and 167 had revised (R)-high-risk disease.
After a median follow-up of 58.7 months, measurable residual disease (MRD)-negativity rate (at the 10−5 threshold) was higher with D-VRd versus VRd in SR (64% vs 38%; P<0.0001) and R-SR (68% vs 38%; P<0.0001) patients. MRD negativity was not statistically different in high-risk (48% vs 56%) and R-high-risk (55% vs 45%) patients.
D-VRd improved the sustainability of MRD-negativity rate (10−5) at one or more years compared with VRd in SR (51% vs 26%; P<0.0001) and R-SR (54% vs 24%; P<0.0001) patients; these results were statistically comparable in high-risk (40% vs 37%) and R-high-risk (43% vs 30%) patients.
Progression-free survival (PFS) improved in the D-VRd group versus VRd in SR (hazard ratio [HR], 0.61; P=0.0136) and R-SR (HR, 0.54; P=0.0189) patients. PFS was comparable between treatment arms in high-risk (HR, 0.88) and R-high-risk (HR, 0.73) patients.
Patients achieving a complete response or better improved with D-VRd in SR and R-SR patients; this was comparable in high-risk and R-high-risk patients.
The study is limited by its small patient population. The study was also underpowered for high-risk patients.
This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting.
Reference
Usmani SZ, Bahlis NJ, Facon T, et al. Daratumumab + bortezomib, lenalidomide, and dexamethasone (D-VRd) vs VRd in transplant-ineligible (TIE)/transplant-deferred (TD) newly diagnosed multiple myeloma (NDMM): phase 3 CEPHEUS trial cytogenetic subgroup analysis. Abstract #MM-739. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, Texas.
Visit the SOHO 2025 meeting news page for more coverage from the meeting.
