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. 2024 Feb;41(2):696-715.
doi: 10.1007/s12325-023-02738-0. Epub 2023 Dec 19.

Comparative Effectiveness of Teclistamab Versus Real-World Physician's Choice of Therapy in LocoMMotion and MoMMent in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Philippe Moreau  1 , María-Victoria Mateos  2 , Maria Esther Gonzalez Garcia  3 , Hermann Einsele  4 , Valerio De Stefano  5 , Lionel Karlin  6 , Joanne Lindsey-Hill  7 , Britta Besemer  8 , Laure Vincent  9 , Suriya Kirkpatrick  10 , Michel Delforge  11 , Aurore Perrot  12 , Niels W C J van de Donk  13 , Charlotte Pawlyn  14 , Salomon Manier  15 , Xavier Leleu  16 , Joaquin Martinez-Lopez  17 , Francesca Ghilotti  18 , Joris Diels  19 , Raúl Morano  20 , Claire Albrecht  21 , Vadim Strulev  19 , Imène Haddad  21 , Lixia Pei  22 , Rachel Kobos  22 , Jennifer Smit  23 , Mary Slavcev  24 , Alexander Marshall  22 , Katja Weisel  25
Affiliations

Comparative Effectiveness of Teclistamab Versus Real-World Physician's Choice of Therapy in LocoMMotion and MoMMent in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Philippe Moreau et al. Adv Ther. 2024 Feb.

Abstract

Introduction: Teclistamab is the first approved B cell maturation antigen × CD3 bispecific antibody with precision dosing for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). We compared the effectiveness of teclistamab in MajesTEC-1 versus real-world physician's choice of therapy (RWPC) in patients from the prospective, non-interventional LocoMMotion and MoMMent studies.

Methods: Patients treated with teclistamab from MajesTEC-1 (N = 165) were compared with an external control arm from LocoMMotion (N = 248) or LocoMMotion + MoMMent pooled (N = 302). Inverse probability of treatment weighting adjusted for imbalances in prognostic baseline characteristics. The relative effect of teclistamab versus RWPC for overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate was estimated with an odds ratio using weighted logistic regression transformed into a response-rate ratio (RR) and 95% confidence interval (CI). Weighted proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results: Baseline characteristics were well balanced between treatment cohorts after reweighting. Patients treated with teclistamab had significantly improved outcomes versus RWPC in LocoMMotion: ORR (RR [95% CI], 2.44 [1.79-3.33]; p < 0.0001), ≥ VGPR (RR 5.78 [3.74-8.93]; p < 0.0001), ≥ CR (RR 113.73 [15.68-825.13]; p < 0.0001), DOR (HR 0.39 [0.24-0.64]; p = 0.0002), PFS (HR 0.48 [0.35-0.64]; p < 0.0001), and OS (HR 0.64 [0.46-0.88]; p = 0.0055). Teclistamab versus RWPC in LocoMMotion + MoMMent also had significantly improved outcomes: ORR (RR 2.41 [1.80-3.23]; p < 0.0001), ≥ VGPR (RR 5.91 [3.93-8.88]; p < 0.0001), ≥ CR (RR 132.32 [19.06-918.47]; p < 0.0001), DOR (HR 0.43 [0.26-0.71]; p = 0.0011), PFS (HR 0.49 [0.37-0.66]; p < 0.0001), and OS (HR 0.69 [0.50-0.95]; p = 0.0247).

Conclusion: Teclistamab demonstrated significantly improved effectiveness over RWPC in LocoMMotion ± MoMMent, emphasizing its clinical benefit as a highly effective treatment for patients with TCE RRMM.

Trial registration: MajesTEC-1, ClinicalTrials.gov NCT03145181 (phase 1) and NCT04557098 (phase 2); LocoMMotion, ClinicalTrials.gov NCT04035226; MoMMent, ClinicalTrials.gov NCT05160584.

Keywords: LocoMMotion; MajesTEC-1; MoMMent; Relapsed or refractory multiple myeloma; Teclistamab; Triple-class exposed.

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Conflict of interest statement

Philippe Moreau: served in a consulting/advisory role and has received honoraria from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Oncopeptides and Sanofi. María-Victoria Mateos: served in a consulting/advisory role for AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen-Cilag, Pfizer, Regeneron, Roche/Genentech, and Takeda; and has received honoraria from AbbVie/Genentech, Amgen, Celgene, GlaxoSmithKline, Janssen-Cilag, Sanofi and Takeda. Maria Esther Gonzalez Garcia: no conflicts of interest to disclose. Hermann Einsele: received research funding or honoraria from and has served as a consultant or adviser for Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen and Sanofi. Valerio De Stefano: served on an advisory board or speakers’ bureau and received honoraria from AbbVie, Alexion, Amgen, AOP Health, Argenx, Bristol Myers Squibb, Grifols, GlaxoSmithKline, Leo Pharma, Novartis, Novo Nordisk, Sanofi, SOBI and Takeda. Lionel Karlin: has served in a consulting/advisory role for Amgen, Janssen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Sanofi, Stemline, Takeda and AbbVie; received honoraria from AbbVie, Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, Stemline and Takeda; has received travel expenses from Amgen, Celgene/Bristol Myers Squibb, Janssen, Sanofi and Takeda; and has an immediate family member employed by Laboratoire Aguettant. Joanne Lindsey-Hill: has received consulting fees from AbbVie and received travel expenses from Janssen. Britta Besemer: received travel, accommodations, and expenses and received honoraria from Amgen, GlaxoSmithKline and Janssen-Cilag. Laure Vincent: received funding from Janssen; received honoraria for consulting/advisory role from Bristol Myers Squibb and Janssen; received travel expenses from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi and Takeda; and has participated in a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb, Janssen and Takeda. Suriya Kirkpatrick: received honoraria from Celgene/Bristol Myers Squibb; received travel expenses from AbbVie, Celgene/Bristol Myers Squibb and Janssen; participated in a Data Safety Monitoring Board or Advisory Board for Celgene; and served in a leadership or fiduciary role for UKONS Research MIG and UK Lung Cancer Nurses RIG. Michel Delforge: served in a consulting/advisory role for Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, Stemline and Takeda; and has received research funding from Janssen. Aurore Perrot: served in a consulting role and received honoraria from AbbVie, Amgen, Celgene, Janssen-Cilag, Pfizer, Sanofi and Takeda. Niels W.C.J. van de Donk: served in a consulting/advisory role for AbbVie, Adaptive Biotechnologies, Amgen, Bayer, Bristol Myers Squibb, Celgene, Janssen, Novartis, Pfizer, Roche, Servier and Takeda; and has received research funding from Amgen, Bristol Myers Squibb, Celgene, Cellectis, Janssen and Novartis. Charlotte Pawlyn: received honoraria from AbbVie, Amgen, Celgene/Bristol Myers Squibb, Janssen, Pfizer, Sanofi and Takeda. Salomon Manier: received research funding from AbbVie, Celgene/Bristol Myers Squibb, Janssen, Novartis and Takeda. Xavier Leleu: held a consulting or advisory role for AbbVie, Amgen, Bristol Myers Squibb, CARsgen, Celgene, Gilead, GlaxoSmithKline, Janssen-Cilag, Karyopharm, Merck, Novartis, Oncopeptides, Roche and Takeda; received travel, accommodations and/or expenses from Takeda; and received honoraria from AbbVie, Amgen, Bristol Myers Squibb, CARsgen, Celgene, GlaxoSmithKline, Janssen-Cilag, Karyopharm, Merck, Novartis, Oncopeptides, Roche, Sanofi and Takeda. Joaquin Martinez-Lopez: has served in a consulting or advisory role, received speakers’ bureau fees and research funding from Bristol Myers Squibb, Janssen and Novartis. Francesca Ghilotti, Joris Diels, Raúl Morano, Imène Haddad, Lixia Pei, Rachel Kobos, Jennifer Smit, Mary Slavcev and Alexander Marshall: employed by Janssen. Claire Albrecht and Vadim Strulev: employed by and own stock in Janssen. Katja Weisel: served as a consultant for and received honoraria from Adaptive Biotechnologies, Karyopharm and Takeda; has received honoraria from Roche; and has received honoraria and served as a member on boards of directors and/or advisory committees for Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Oncopeptide and Sanofi.

Figures

Fig. 1
Fig. 1
Unadjusted and ATT-adjusted response rates for teclistamab versus LocoMMotion versus pooled LocoMMotion + MoMMent. aORR =  ≥ CR + VGPR + PR; may not sum appropriately as shown because of rounding. bTeclistamab versus LocoMMotion. cTeclistamab vs LocoMMotion + MoMMent. ATT average treatment effect in the treated, CI confidence interval, ≥ CR complete response or better, ORR overall response rate, PR partial response, RR response-rate ratio, RWPC real-world physician’s choice of therapy, ≥ VGPR very good partial response or better
Fig. 2
Fig. 2
Base case adjusted (ATT weighted) Kaplan–Meier plots for a DOR, b PFS, and c OS for teclistamab versus LocoMMotion versus pooled LocoMMotion + MoMMent. ATT average treatment effect in the treated, CI confidence interval, DOR duration of response, NE not evaluable, OS overall survival, PFS progression-free survival
See this image and copyright information in PMC

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