Presentation (CTI)

OBJECTIVES: In Phase 3 IMROZ trial, isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd) significantly improved progression-free survival (PFS) by 40.4% vs VRd in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant. At median follow-up of 59.7 months, 26.0% patients in the IVRd group and 32.6% patients in the VRd group had died, and the follow-up is ongoing. At the final analysis of Phase 3 MAIA trial, daratumumab in combination with lenalidomide and dexamethasone (DRd) showed significant improvement in PFS and overall survival (OS) vs Rd during median follow-up of 7.5 years. In the absence of head-to-head comparison, a matching-adjusted indirect comparison (MAIC) was conducted to assess the efficacy of IVRd versus DRd.
METHODS: Patient-level data of IVRd from IMROZ (n=265) and aggregate data of DRd from MAIA (n=368) were used to perform an unanchored MAIC. Matched characteristics included age, ISS stage, ECOG PS, cytogenetic risk, MM type, and creatinine clearance. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the weighted Cox proportional hazard models. Mean difference in restricted mean survival time (RMST) was estimated.
RESULTS: After matching, all available baseline characteristics were well balanced between treatments. In the MAIC, IVRd showed significantly better PFS compared to DRd (HR= 0.74; 95% CI: 0.60−0.96) and a numeric trend of improvement in OS (HR= 0.91; 95% CI: 0.68−1.17). The mean (95% CI) difference in RSMT was 4.25 (-0.05, 8.54) months for PFS and 1.29 months (-2.55, 5.12) for OS.
CONCLUSIONS: This MAIC demonstrated significant improvement in PFS for IVRd vs DRd and a numeric trend in favor of IVRd for OS. As OS results from IMROZ remain immature, future analysis is warranted when long-term survival data becomes available. Given the superior PFS outcome vs DRd, IVRd becomes a valuable option for transplant-ineligible NDMM.