Multinational phase 3 study of D-VRd versus VRd voor transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma

The multinational phase 3 CEPHEUS study evaluated addition of daratumumab (D) to bortezomib-lenalidomide-dexamethasone (VRd) for newly diagnosed multiple myeloma (NDMM) patients who did not undergo transplantation. Patients were randomized 1:1 to eight cycles of C-VRd or VRd followed by D-Rd or Rd until progression. Primary endpoint was MRD-negativity rate at 10^-5. At a median follow-up of 58.7 months, the MRD-negativity rate was 60.9% with D-VRd versus 39.4% with VRd (OR 2.37; p<0.0001). Rates of complete response or better (81.2% versus 61.6%; p<0.0001) and sustained MRD negativity (≥ 12 months; 48.7% versus 26.3%; p<0.0001) were significantly higher with D-VRd versus VRd. Risk of progression or death was 43% lower for D-VRd versus VRd (HR 0.57; p=0.0005). Adverse events were consistent with the known safety profiles of daratumumab and VRd. The authors conclude that among transplant-ineligible or transplant-deferred NDMM patients, combined D plus VRd produced deeper and more durable MRD responses versus VRd alone.