Updated Results of a Matching-Adjusted Indirect Comparison of Elranatamab Versus Teclistamab in Patients with Triple-Class Exposed/Refractory Multiple Myeloma

Introduction Elranatamab (ELRA) is a BCMAxCD3 bispecific antibody approved for the treatment of relapsed refractory multiple myeloma (RRMM) based on the demonstrated efficacy and safety in MagnetisMM-3 trial (MM-3; NCT04649359). Teclistamab (TEC), another approved BCMAxCD3 bispecific antibody, demonstrated efficacy in the MajecTEC-1 trial (NCT04557098). In the absence of head-to-head trials, an unanchored matching-adjusted indirect treatment comparison (MAIC) assessed their relative efficacy (Mol et al., 2024). Here, we update the results based on a longer follow-up of the MM-3 and MajesTEC-1 trials. Methods Individual patient data from MM-3 (28.4-month follow-up; BCMA naive, N=123) were reweighted to match published aggregated data from MajesTEC-1 (30.4-month follow-up; N=165). Eligibility criteria were similar, with two exceptions: MM-3 enrolled patients who were triple-class refractory, while MajesTEC-1 enrolled patients who were TCE. MajesTEC-1 also excluded patients with Eastern Cooperative Oncology Group (ECOG) performance score (PS) >1; therefore, patients with ECOG PS 2 in MM-3 were removed from the analysis (n=7). Key baseline characteristics were chosen for adjustment to account for cross-trial differences. The baseline characteristics for MajesTEC-1 were referenced from Moreau et al (2022). These variables were identified through univariate Cox regressions using the MM-3 individual patient data (IPD), a systematic literature review, and validation by clinical experts. Variables included age, sex (overall survival (OS) only), median time since diagnosis, International Staging System (ISS) disease stage, high-risk cytogenetics, extramedullary disease, number of prior lines of therapy, ECOG PS, and penta-exposed/refractory status. A sensitivity analysis was conducted in which a random sample of the observations in MM-3 imputed missing values of the adjusted baseline characteristics for ELRA. The unanchored MAIC analyses followed the code provided in the National Institute for Health and Care Excellence Decision Support Unit 18 by Phillippo et al, 2016. Efficacy outcomes included progression-free survival (PFS), OS, and duration of response (DoR). Additionally, efficacy outcomes among patients who achieved a complete response (CR) or higher were also included. Results were presented in hazard ratios (HR) with 95% confidence intervals (CIs). Results After adjustment, the distributions of confounding variables were identical between ELRA and TEC. For PFS and DoR, the post-matching effective sample size (ESS) for ELRA was 76 in the base case and 91 in the sensitivity analysis. For OS, the ESSs were 74 and 87, respectively. Compared with TEC, ELRA was associated with a significantly longer PFS (base case HR=0.55 [95% CI 0.37-0.81], p<.05; sensitivity analysis HR=0.56 [0.39-0.82], p<.05), a significantly longer OS (base case HR=0.60 [0.40-0.91], p<.05; sensitivity analysis HR=0.69 [0.47-1.01], p=.06), and a significantly longer DoR (base case HR=0.56 [0.31-0.99], p<.05; sensitivity analysis HR=0.58 [0.33-0.99], p<.05). Among patients who achieved ≥CR, ELRA was associated with a significantly longer PFS (base case HR=0.28 [0.11-0.74], p<.05; sensitivity analysis HR=0.24 [0.09-0.60], p<.05), a significantly longer OS (base case HR=0.35 [0.13-0.96], p<.05; sensitivity analysis HR=0.43 [0.17-1.09], p=0.07) and a significantly longer DoR (base case HR=0.28 [0.11-0.75], p<.05; sensitivity analysis HR=0.24 [0.09-0.61], p<.05), compared with TEC. Conclusions In the updated MAIC with over 28 months of follow-up for both ELRA and TEC, ELRA consistently demonstrated significantly longer OS, PFS, and DoR vs. TEC. Among patients who achieved ≥CR, ELRA showed significantly longer OS, PFS, and DoR. These results suggest that ELRA continues to be an effective option for treating patients with TCE MM. Study sponsor: Pfizer.