Phase 3 MonumenTAL-3: talquetamab plus daratumumab extends progression-free survival in relapsed or refractory multiple myeloma (HR 0.28)

In the randomized phase 3 MonumenTAL-3 trial (864 patients with relapsed or refractory multiple myeloma after at least one prior line, 287 per arm), the GPRC5D-directed bispecific antibody talquetamab — combined with daratumumab and pomalidomide or with daratumumab alone — outperformed daratumumab-pomalidomide-dexamethasone. At 24 months, progression-free survival was 81.3% and 77.6% versus 51.2% (HR 0.28; 95% CI 0.20-0.40 and HR 0.33; 0.24-0.46; P<0.001), complete response or better was reached by 71.1% and 69.0% versus 34.5% of patients, and MRD negativity by 52.3% and 46.3% versus 15.9%. Overall survival at 24 months was 89.2% and 87.9% versus 79.1% (hazard ratios for death 0.47 and 0.51), with serious adverse events more frequent in the talquetamab arms (63.0% versus 52.6% and 53.7%) and fatal adverse events less frequent (1.8% versus 4.0% and 4.6%). The trial did not compare these regimens with BCMA-directed T-cell-redirecting therapies, so the sequencing of the two drug classes remains unresolved.