Teclistamab in Relapsed or Refractory Multiple Myeloma
Philippe Moreau, Alfred L Garfall, Niels W C J van de Donk, Hareth Nahi, Jesús F San-Miguel, Albert Oriol, Ajay K Nooka, Thomas Martin, Laura Rosinol, Ajai Chari, Lionel Karlin, Lotfi Benboubker, Maria-Victoria Mateos, Nizar Bahlis, Rakesh Popat, Britta Besemer, Joaquín Martínez-López, Surbhi Sidana, Michel Delforge, Lixia Pei, Danielle Trancucci, Raluca Verona, Suzette Girgis, Shun X W Lin, Yunsi Olyslager, Mindy Jaffe, Clarissa Uhlar, Tara Stephenson, Rian Van Rampelbergh, Arnob Banerjee, Jenna D Goldberg, Rachel Kobos, Amrita Krishnan, Saad Z Usmani, Philippe Moreau, Alfred L Garfall, Niels W C J van de Donk, Hareth Nahi, Jesús F San-Miguel, Albert Oriol, Ajay K Nooka, Thomas Martin, Laura Rosinol, Ajai Chari, Lionel Karlin, Lotfi Benboubker, Maria-Victoria Mateos, Nizar Bahlis, Rakesh Popat, Britta Besemer, Joaquín Martínez-López, Surbhi Sidana, Michel Delforge, Lixia Pei, Danielle Trancucci, Raluca Verona, Suzette Girgis, Shun X W Lin, Yunsi Olyslager, Mindy Jaffe, Clarissa Uhlar, Tara Stephenson, Rian Van Rampelbergh, Arnob Banerjee, Jenna D Goldberg, Rachel Kobos, Amrita Krishnan, Saad Z Usmani
Abstract
Background: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.
Methods: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better).
Results: Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2).
Conclusions: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).
Copyright © 2022 Massachusetts Medical Society.
Figures
References
- Yong K, Delforge M, Driessen C, et al. Multiple myeloma: patient outcomes in real-world practice. Br J Haematol 2016;175:252–64.
- Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Hemasphere 2021;5(2):e528.
- Kumar SK, Callander NS, Adekola K, et al. Multiple myeloma, version 3.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2020;18:1685–717.
- Mateos M-V, Weisel K, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia 2022;36:1371–6.
- Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol 2020;21:207–21.
- Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021;384:705–16.
- Shah N, Chari A, Scott E, Mezzi K, Usmani SZ. B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. Leukemia 2020;34:985–1005.
- Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 2021;398:314–24.
- Usmani SZ, Garfall AL, van de Donk NWCJ, et al. Teclistamab, a B-cell maturation antigen χ CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet 2021;398:665–74.
- Rajkumar SV, Harousseau J-L, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 2011;117:4691–5.
- Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17(8):e328–e346.
- Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 2019;25:625–38.
- Girgis S, Lin SXW, Pillarisetti K, et al. Teclistamab and talquetamab modulate levels of soluble B-cell maturation antigen in patients with relapsed and/or refractory multiple myeloma. J Clin Oncol 2021;39:Suppl:8047. abstract.
- Munshi NC, Avet-Loiseau H, Anderson KC, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv 2020;4:5988–99.
- San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood 2022;139:492–501.
- Kiss S, Gede N, Hegyi P, et al. Addition of daratumumab to multiple myeloma backbone regimens significantly improves clinical outcomes: a systematic review and meta-analysis of randomised controlled trials. Sci Rep 2021;11:21916.
- Rosiñol L, Beksac M, Zamagni E, et al. Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment consid-erations. Br J Haematol 2021;194:496–507.
- Pillarisetti K, Powers G, Luistro L, et al. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv 2020;4:4538–49.
- Huehls AM, Coupet TA, Sentman CL. Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol 2015;93:290–6.
- Strohl WR, Naso M. Bispecific T-cell redirection versus chimeric antigen receptor (CAR)-T cells as approaches to kill cancer cells. Antibodies (Basel) 2019;8:41.
- Hutchings M, Mous R, Clausen MR, et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet 2021;398:1157–69.
- Moreau P, Usmani SZ, van de Donk NWCJ, et al. Matching-adjusted indirect treatment comparison (MAIC) of teclistamab (tec) versus belantamab mafodotin (belamaf) for the treatment of patients (pts) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). J Clin Oncol 2022;40:8035. abstract.
- Nucci M, Anaissie E. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis 2009;49:1211–25.
- Vijenthira A, Gong IY, Fox TA, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 2020;136:2881–92.
Source: PubMed