Elranatamab versus physician’s choice of treatment in patients with triple-class exposed/refractory multiple myeloma: an updated matching-adjusted indirect comparison

Abstract

Aim: Despite the availability of novel treatment options for patients with triple-class exposed/refractory multiple myeloma, there is a lack of consensus on the optimal regimen. A previous unanchored matching-adjusted indirect comparison (MAIC) of the MagnetisMM-3 (NCT04649359) and LocoMMotion (NCT040 35226) study reported significant improvements in progression-free survival (PFS) and overall survival (OS) with elranatamab versus physician’s choice of treatment. Materials & methods: We conducted an updated MAIC based on more recent data (28.4 months for MagnetisMM-3). Following reweighting of MagnetisMM-3 individual patient data to match the LocoMMotion population, the effective sample size was 64 for PFS and 63 for OS in the base-case analysis. Results: Consistent with the original MAIC, significantly improved PFS (hazard ratio [HR] [95% confidence interval (CI)]: 0.32 [0.21, 0.50], p < 0.01) and OS (HR [95% CI]: 0.50 [0.33, 0.78], p < 0.01) were observed with elranatamab versus physician’s choice of treatment. The robustness of the results was demonstrated in sensitivity analyses in which missing baseline characteristics data for elranatamab were imputed. Conclusion: Overall, the findings of this study align with and add confidence to the conclusions of the previous MAIC that elranatamab is associated with significantly improved outcomes versus standard treatment, supporting the value to elranatamab for the treatment of patients with triple-class exposed/refractory multiple myeloma. Plain language summary What is this article about? Multiple myeloma (MM) is a blood cancer that becomes harder to treat after multiple therapies stop working. Patients with triple-class exposed/refractory (TCE/R) MM have already received treatments from the three main drug classes used for MM, but their cancer has either not responded or has come back. These patients have very few treatment options and tend to have poor outcomes. Elranatamab is a type of treatment called a bispecific antibody, which helps the immune system recognize and attack MM cells in patients with TCE/R MM. This study indirectly compared elranatamab to a physician’s choice of treatment (PCT) based on data from a prospective study LocoMMotion. Since there are no clinical trials that directly compare elranatamab to PCT, a methodology known as matching-adjusted indirect comparison was conducted. This method helps account for differences between the patient groups in the two studies, making the comparison as fair and accurate as possible. What were the results? The results showed that elranatamab had significantly longer survival outcomes compared with PCT, based on longer-term follow-up data from the elranatamab clinical trial. What do the results mean? These findings suggest that elranatamab may be a more effective treatment option than current standard therapies for patients with TCE/R MM.