A matching-adjusted indirect comparison of the efficacy of elranatamab versus physician’s choice of treatment in patients with triple-class exposed/refractory multiple myeloma

Abstract

Introduction For patients with triple-class exposed/refractory multiple myeloma (TCE/R MM), prognosis is poor and effective treatment options are limited. Elranatamab is a novel B-cell maturation antigen (BCMA)- and CD3-directed bispecific antibody which was approved by the US Food and Drug Administration in August 2023 and demonstrated safety and efficacy in patients with TCE/R MM in the phase 2, single-arm MagnetisMM-3 trial (NCT04649359). To compare the effectiveness of elranatamab vs physician’s choice of treatment (PCT) in the absence of head-to-head comparative data, a matching-adjusted indirect comparison (MAIC) was conducted. Methods Individual patient data from MagnetisMM-3 (Cohort A [BCMA-naïve] N = 123, 14.7 months of follow-up) were reweighted to match published summary data from two real-world studies of PCT in patients with TCE/R MM (LocoMMotion and MAMMOTH) using a propensity score-type logistic regression. Unanchored MAIC analyses were conducted according to National Institute for Health and Care Excellence (NICE) Decision Support Unit (DSU) 18 guidance. Results Compared with PCT in LocoMMotion, elranatamab was associated with a significantly higher objective response rate (ORR rate difference: 37.52; 95% CI 26.20–48.83; odds ratio: 4.85; 95% CI 2.85–8.23) and complete or stringent complete response rate (≥CR rate difference: 42.29; 95% CI 31.84–52.74; odds ratio: 184.01; 95% CI 24.66–1372.86), longer progression-free survival (PFS HR 0.32; 95% CI 0.20–0.49), and overall survival (OS HR 0.62; 95% CI 0.40–0.94). Compared with PCT in MAMMOTH, elranatamab was associated with significantly higher ORR (rate difference: 28.14; 95% CI 16.77–39.52; odds ratio: 3.24; 95% CI 1.98–5.32) and ≥ CR (rate difference: 26.22; 95% CI 16.40–36.05; odds ratio: 5.48; 95% CI 2.88–10.44), as well as longer PFS (HR 0.25; 95% CI 0.17–0.37) and OS (HR 0.49; 95% CI 0.33–0.71). Sensitivity analysis results were consistent with the base case. Conclusion In the MAIC, elranatamab was consistently associated with improved rates and depth of response and significantly longer PFS and OS versus PCT in LocoMMotion and MAMMOTH.