Multinational phase 3 trial of DVRd versus VRd for NDMM: transplant-ineligible subgroup analysis of CEPHEUS

In the multinational phase 3 CEPHEUS trial, transplant-ineligible (TIE) or transplant-deferred patients with newly diagnosed multiple myeloma (NDMM) were randomized to daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) or VRd alone. Results from the TIE subgroup (n= 289; DVRd n=144; VRd n=145) have now been published. Patients were either aged 18-70 years with at least one comorbidity likely to negatively affect tolerablility of high-dose chemotherapy wit ASCT or aged ≥ 70 years. At a median follow-up of 58.7 months, minimal residual disease (MRD)-negativity rate (10^-5) was 60.4% (DVRd) versus 39.3% (VRd) while the sustained MRD-negativity rate (10^-6) was 45.8% versus 26.9%, respectively. Risk of disease progression or death was 49% lower with DVRd than with VRd (HR 0.51; p=0.0003). Although immature, overall survival favored DVRd (HR 0.66; 95% CI 0.42-1.03). Adverse events were consistent with know safety profiles. The authors conclude that this analysis demonstrates that the deep responses achieved with DVRd translate into improved progression-free survival in patients with TIE NDMM