Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D‐VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant‐eligible patients with newly diagnosed multiple myeloma, using propensity score matching

BACKGROUND: Traditional bortezomib, thalidomide, and dexamethasone (VTd) regimens for patients with newly diagnosed multiple myeloma (NDMM) include doses of thalidomide up to 200 mg/day (VTd‐label). Clinical practice has evolved to use a lower dose (100 mg/day) to reduce toxicity (VTd‐mod), which was evaluated in the phase III CASSIOPEIA study, without or with daratumumab (D‐VTd; an anti‐CD38 monoclonal antibody). We used propensity score matching to compare efficacy and safety for VTd‐mod and D‐VTd with VTd‐label. METHODS: Patient‐level data for VTd‐mod and D‐VTd from CASSIOPEIA (NCT02541383) and data for VTd‐label from the PETHEMA/GEM study (NCT00461747) were analyzed. Propensity scores were estimated using logistic regression, and nearest‐neighbor matching procedure was used. Outcomes included overall survival (OS), progression‐free survival (PFS), time to progression (TTP), postinduction and posttransplant responses, as well as rate of treatment discontinuation and grade 3/4 peripheral neuropathy. RESULTS: VTd‐mod was noninferior to VTd‐label for OS, PFS, TTP, postinduction very good partial response or better (≥VGPR) and overall response rate (ORR). VTd‐mod was significantly better for posttransplant ≥VGPR and ORR versus VTd‐label. VTd‐mod safety was not superior to VTd‐label despite the lower thalidomide dose. D‐VTd was significantly better than VTd‐label for OS, PFS, TTP, postinduction and posttransplant ≥VGPR and ORR, and was noninferior to VTd‐label for safety outcomes. CONCLUSIONS: In transplant‐eligible patients with NDMM, D‐VTd had superior efficacy compared with VTd‐label. Despite a lower dose of thalidomide, VTd‐mod was noninferior to VTd‐label for safety and was significantly better for posttransplant ≥VGPR/ORR. These data further support the first‐line use of daratumumab plus VTd.