D-VRd doubles sustained MRD negativity vs VRd in transplant-ineligible/deferred NDMM

Daratumumab is an anti-CD38 monoclonal antibody added to bortezomib/lenalidomide/dexamethasone to create a quadruplet regimen for newly diagnosed multiple myeloma patients who are transplant-ineligible or transplant-deferred. In the randomized Phase III CEPHEUS trial (NCT03652064; n=395; D-VRd n=197 vs VRd n=198; median follow-up 58.7 months), D-VRd improved MRD negativity by NGS at both 10^-5 (60.9% vs 39.4%; OR 2.37; p<0.0001) and 10^-6 (46.2% vs 27.3%; OR 2.24; p=0.0001), and sustained MRD negativity ≥12 months also favored D-VRd at 10^-5 (49.2% vs 27.3%) and 10^-6 (34.0% vs 16.2%). Overall CEPHEUS PFS favored D-VRd with HR 0.57 (p=0.0005), improving on the VRd backbone that delivered median PFS ~43 months vs ~30 months with Rd in SWOG S0777; among patients who achieved MRD negativity, PFS numerically favored D-VRd but did not reach statistical significance, and adverse events were broadly consistent with known daratumumab/VRd safety.