Publicaciones científicas
Teclistamab in Relapsed or Refractory Multiple Myeloma
Philippe Moreau 1 , Alfred L Garfall 1 , Niels W C J van de Donk 1 , Hareth Nahi 1 , Jesús F San-Miguel 1 , Albert Oriol 1 , Ajay K Nooka 1 , Thomas Martin 1 , Laura Rosinol 1 , Ajai Chari 1 , Lionel Karlin 1 , Lotfi Benboubker 1 , Maria-Victoria Mateos 1 , Nizar Bahlis 1 , Rakesh Popat 1 , Britta Besemer 1 , Joaquín Martínez-López 1 , Surbhi Sidana 1 , Michel Delforge 1 , Lixia Pei 1 , Danielle Trancucci 1 , Raluca Verona 1 , Suzette Girgis 1 , Shun X W Lin 1 , Yunsi Olyslager 1 , Mindy Jaffe 1 , Clarissa Uhlar 1 , Tara Stephenson 1 , Rian Van Rampelbergh 1 , Arnob Banerjee 1 , Jenna D Goldberg 1 , Rachel Kobos 1 , Amrita Krishnan 1 , Saad Z Usmani 1
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, 77.8% 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.).
CITA DEL ARTÍCULO N Engl J Med. 2022 Aug 11;387(6):495-505. doi: 10.1056/NEJMoa2203478. Epub 2022 Jun 5.
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