Updated Results of a Matching-Adjusted Indirect Comparison of Elranatamab Versus Physician's Choice of Treatment in Patients with Triple-Class Exposed/Refractory Multiple Myeloma

Introduction

For patients with triple-class exposed multiple myeloma (TCE MM), the prognosis is poor, and limited effective treatment options are available. Elranatamab (ELRA) is a bispecific antibody that demonstrated efficacy and safety in patients with TCE MM in the phase 2, single-arm MagnetisMM-3 trial (NCT04649359). ELRA is approved for the treatment of relapsed refractory multiple myeloma (RRMM) in the United States. To compare the effectiveness of ELRA vs. physician's choice of treatment (PCT) in the absence of comparative data, a matching-adjusted indirect comparison (MAIC) was conducted (Mol et al., 2024). Here, we update the MAIC results based on longer follow-up from the MagnetisMM-3 trial.

Methods

Individual patient data from MagnetisMM-3 (28.4-month follow-up; BCMA naive, N=123) were reweighted to match published summary data from LocoMMotion ([NCT04035226]), an ongoing, prospective, non-interventional study of PCT in patients with TCE MM (N=248).

Key baseline characteristics were chosen for adjustment to account for cross-trial differences. The baseline characteristics for LocoMMotion were referenced from Mateos 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, extramedullary disease, number of prior lines of therapy, Eastern Cooperative Oncology Group (ECOG) performance score, creatinine clearance, and penta-refractory status. A sensitivity analysis was conducted in which a random sample of the observations in MagnetisMM-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) and OS. Results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

After adjustment, the selected key baseline characteristics were matched between ELRA and PCT. For PFS, the post-matching effective sample size (ESS) for ELRA was 64 in the base case and 70 in the sensitivity analysis. For OS, the ESSs were 63 and 69, respectively. Compared with PCT, ELRA was associated with a significantly longer PFS (base case HR=0.32, 95% CI: [0.21-0.50], p≤.01; sensitivity analysis HR=0.29 [0.19-0.43], p≤.01) and a significantly longer OS (base case HR=0.50 [0.33-0.78], p≤.01; sensitivity analysis HR = 0.48 [0.32-0.72], p≤.01).

Conclusions

In the updated MAIC with over 28 months of follow-up, ELRA consistently demonstrated significantly longer PFS and OS compared with PCT used in the real world. These results suggest that elranatamab offers significantly improved outcomes compared with standard treatment for patients with TCE MM.

Study sponsor: Pfizer.

Mol:Pfizer Inc: Consultancy. Hu:Pfizer Inc: Consultancy. LeBlanc:Pfizer: Consultancy, Honoraria; Novartis: Consultancy; BMS/Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Rigel: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria; Gilead: Consultancy; Astellas: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Lilly: Consultancy, Honoraria; Menarini/Stemline: Consultancy; Incyte: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria; Jazz Pharmaceuticals: Research Funding; Apellis: Consultancy; Agios/Servier: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Dosentrx: Current holder of stock options in a privately-held company; ThymeCare: Current holder of stock options in a privately-held company. Cappelleri:Pfizer: Current Employment, Current equity holder in publicly-traded company. Chu:Pfizer Inc: Current Employment. Nador:Pfizer Ltd, Surrey, UK: Current Employment, Current holder of stock options in a privately-held company. Aydin:Pfizer Inc: Current Employment, Current holder of stock options in a privately-held company. Perez-Cruz:Pfizer Inc: Current Employment, Current holder of stock options in a privately-held company. Hlavacek:Pfizer Inc, New York, NY, USA: Current Employment, Current holder of stock options in a privately-held company.