Daratumumab for Newly Diagnosed Multiple Myeloma

Triplet therapy with bortezomib, lenalidomide, and dexamethasone (VRd), followed by autologous stem-cell transplant (ASCT) and lenalidomide maintenance is a standard of care for transplant-eligible myeloma patients. Investigators now report an industry-sponsored, multicenter, phase 3 trial comparing VRd to VRd plus the anti-CD38 antibody daratumumab (D-VRd) administered subcutaneously (1800 mg) with induction (4 cycles), post-ASCT consolidation (2 cycles), and lenalidomide maintenance therapy until disease progression.

A total of 709 transplant-eligible patients aged 18–70 years were randomized; 9 (1.3%) were Black and 10 (1.4%) were Asian. At a median follow-up of 48 months, the primary endpoint — progression-free survival (PFS) — was significantly better in the D-VRd group (hazard ratio for disease progression or death, 0.42). Estimated PFS rates were 84% in the D-VRd group versus 68% in the VRd group. Two key secondary endpoints — complete response or better and minimal residual disease (MRD)–negative status — also favored D-VRd. Data on overall survival were immature.

The most common grade 3 or 4 adverse events in the D-VRd and VRd groups included neutropenia (62% and 51%, respectively) and thrombocytopenia (29% and 17%). Serious adverse events occurred in 57% of the D-VRd group and 49% of the VRd group, and adverse events leading to treatment discontinuation occurred in 9% and 21%, respectively.