Daratumumab + Carfilzomib/Lenalidomide/Dex Beats KRd Alone for Deep Remission in Newly Diagnosed Myeloma

Daratumumab, an anti-CD38 IgG1κ antibody, was added to the KRd triplet (Carfilzomib/Lenalidomide/Dex) in the randomized phase 2 ADVANCE trial (n=306 NDMM; transplant-eligible and ineligible). In 306 patients with newly-diagnosed multiple myeloma, after 8 cycles, MRD-negativity at 10⁻⁵ by NGS reached 59% vs 33% with KRd (odds ratio 2.9; p < .0001). With 31.2 month median follow-up, 31-month PFS was 92% for daratumumab + KRd triplet vs 83% for KRd, and event-free survival favored the quadruplet (p = .0157). Grade ≥3 toxicities were chiefly neutropenia (10% vs 16%) and pneumonia (9% vs 5%); no new safety signals emerged. By comparison, the earlier GRIFFIN study of daratumumab + VRd reported MRD-negativity ~64% vs 32% for VRd, but at the cost of higher peripheral-neuropathy risk from bortezomib.