Comparative Efficacy of Teclistamab Versus Current Treatments in Real-World Clinical Practice in the Prospective LocoMMotion Study in Patients with Triple-Class-Exposed Relapsed and/or Refractory Multiple Myeloma

Introduction Patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE-RRMM) have a poor prognosis and limited treatment options. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, was studied in patients with TCE-RRMM in the single-arm MajesTEC-1 study. To assess the relative effectiveness of teclistamab versus real-world physician’s choice of therapy (RWPC), adjusted comparisons were performed using individual patient data from MajesTEC-1 and LocoMMotion, a prospective study of patients with TCE-RRMM. Methods An external control arm for MajesTEC-1 was created from patients in LocoMMotion ( n = 248; clinical cut-off: November 2, 2021) and compared with treated patients ( n = 165) from MajesTEC-1 (teclistamab 1.5 mg/kg weekly; clinical cut-off: March 16, 2022). Inverse probability weighting was used to adjust for imbalances in baseline covariates. For binary endpoints [overall response rate (ORR), very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR)], relative effect of teclistamab versus RWPC was estimated with an odds ratio and relative response rate and 95% confidence interval (CI), derived from weighted logistic regression. Weighted Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% CIs for time-to-event endpoints [duration of response (DOR), progression-free survival (PFS), and overall survival (OS)]. Results After weighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, teclistamab-treated patients were 2.3-fold, 5.2-fold and 148.3-fold, more likely to reach ORR [response-rate ratio (RR) = 2.31, 95% CI 1.77–2.85, p < 0.0001], ≥ VGPR (RR = 5.19, 95% CI 3.26–7.12, p < 0.0001) and ≥ CR (RR = 148.25, 95% CI 20.63–1065.40, p < 0.0001), respectively, versus patients receiving RWPC. Following adjustment, DOR (HR 0.32, 95% CI 0.19–0.54, p < 0.0001) and PFS (HR 0.48, 95% CI 0.35–0.65, p < 0.0001) were significantly longer with teclistamab versus RWPC. OS was numerically better with teclistamab versus RWPC [HR 0.77 (0.55–1.09), p = 0.1419]. Conclusion Teclistamab demonstrated improved effectiveness versus RWPC, highlighting its clinical benefit as a novel and effective treatment for patients with TCE-RRMM. Trial Registration Majest TEC-1, ClinicalTrials.gov NCT04557098; LocoMMotion, ClinicalTrials.gov NCT04035226.