Matching‐adjusted indirect comparison of efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) as per label compared with modified VTd dosing schedules in patients with newly diagnosed multiple myeloma who are transplant eligible

BACKGROUND: The combination of bortezomib, thalidomide, and dexamethasone (VTd) is a standard of care for transplant‐eligible patients with newly diagnosed multiple myeloma (NDMM). Although approved labeling for VTd includes an escalating thalidomide dose up to 200 mg daily (VTd‐label), a lower fixed dose of thalidomide (100 mg daily; VTd‐mod) has become commonplace in clinical practice. To date, no clinical trials comparing VTd‐mod with VTd‐label have been performed. Here, we compared outcomes for VTd‐mod with VTd‐label using a matching‐adjusted indirect comparison. METHODS: VTd‐mod data were from NCT02541383 (CASSIOPEIA; phase III) and NCT00531453 (phase II); VTd‐label data were from NCT00461747 (PETHEMA/GEM; phase III). To adjust for heterogeneity, baseline characteristics from VTd‐label were weighted to match VTd‐mod. Outcomes included overall survival (OS), progression‐free survival (PFS), postinduction and posttransplant responses, and safety. RESULTS: VTd‐mod was noninferior to VTd‐label for OS, postinduction overall response rate (ORR), and very good partial response or better (≥VGPR). VTd‐mod was significantly better than VTd‐label for PFS, posttransplant ORR, and ≥VGPR. VTd‐mod was noninferior to VTd‐label for safety outcomes, and inferior to VTd‐label for postinduction and posttransplant complete response or better. CONCLUSIONS: Our analysis supports the continued use of VTd‐mod in clinical practice in transplant‐eligible NDMM patients.