Comparative efficacy of belantamab mafodotin plus bortezomib and dexamethasone (BVd) vs standard of care in patients with relapsed/refractory multiple myeloma (RRMM).

Abstract

7568 Background: BVd is approved in the United States as a third-line or later (3L+) option for patients with RRMM based on the DREAMM-7 study of BVd vs daratumumab (D) plus bortezomib (V) and dexamethasone (d; DVd). This study aimed to compare the relative efficacy of BVd vs pomalidomide (P) plus Vd (PVd), elotuzumab plus Pd (EPd), isatuximab plus Pd (IsaPd), and idecabtagene vicleucel (ide-cel) in adults with 3L+ RRMM who received a proteasome inhibitor and an immunomodulatory drug. In the absence of head-to-head trials, indirect treatment comparisons (ITCs) can inform on the relative efficacy of regimens. Methods: ITCs of progression-free survival (PFS) and overall survival (OS) were conducted using the eligible study populations (only patients with ≥2 prior lines of therapy [LOT]) from the DREAMM-7 (BVd), DREAMM-8 (PVd), ELOQUENT-3 (EPd), ICARIA-MM (IsaPd), and KarMMA-3 (ide-cel) trials. Individual pt data (IPD) were available for patients treated with BVd and PVd, while only published summary data were available for patients treated with EPd, IsaPd, and ide-cel. In base-case analyses, study populations were weighted (using inverse probability of treatment weighting to compare to PVd and matching adjusted indirect comparison for the other treatments) to match in terms of age, prior exposure to bortezomib, prior exposure to lenalidomide, refractoriness to lenalidomide, number of prior LOT, and cytogenetic risk. Weighting was done separately for each comparator treatment. Weighted Cox regression was then performed to compare outcomes of patients treated with BVd to each respective comparator treatment. Results: In the base-case models, weighting yielded very good balance for all matched covariates (standardized mean difference <0.25 for each covariate across each comparison, and <0.10 in all cases except for age, prior bortezomib, and >4 prior LOT in the PVd comparison). Hazard ratios for BVd vs EPd, IsaPd, and ide-cel for PFS and OS significantly favored BVd (Table). For BVd vs PVd, PFS significantly favored BVd and OS numerically favored BVd. Conclusions: In DREAMM-7, direct comparison of BVd vs DVd showed PFS and OS improvements with BVd. This indirect comparison of patients in the 3L+ setting further showed that BVd improved PFS and OS vs PVd, EPd, IsaPd, and ide-cel. Comparison (sample size/effective sample size value) BVd vs PVd (86 and 68/35) BVd vs EPd(103/42 and 60) BVd vs IsaPd(85/52 and 154) BVd vs Ide-cel(96/50 and 254) Outcome PFS OS PFS OS PFS OS PFS OS Hazard ratio 0.517 0.604 0.337 0.405 0.538 0.348 0.468 0.509 95% confidence interval 0.275, 0.972 0.331, 1.103 0.173, 0.654 0.209, 0.787 0.346, 0.836 0.195, 0.623 0.287, 0.762 0.274, 0.945 p-value 0.041 0.101 0.001 0.008 0.006 <0.001 0.002 0.033