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

Philippe Moreau, Niels W. C. J. van de Donk, Michel Delforge, Hermann Einsele, Valerio de Stefano, Aurore Perrot, Britta Besemer, Charlotte Pawlyn, Lionel Karlin, Salomon Manier, Xavier Leleu, Katja Weisel, Francesca Ghilotti, Joris Diels, Ahmed Elsada, Raul Morano, Vadim Strulev, Lixia Pei, Rachel Kobos, Jennifer SmitMary Slavcev, Maria-Victoria Mateos*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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, NCT04557098; LocoMMotion, NCT04035226.

Original languageEnglish
Pages (from-to)2412-2425
Number of pages14
JournalAdvances in therapy
Issue number5
Early online date2023
Publication statusPublished - May 2023

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