1. Teclistamab in Relapsed or Refractory Multiple Myeloma
- Author
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Moreau, Philippe, Garfall, Alfred L, van de Donk, Niels WCJ, Nahi, Hareth, San-Miguel, Jesús F, Oriol, Albert, Nooka, Ajay K, Martin, Thomas, Rosinol, Laura, Chari, Ajai, Karlin, Lionel, Benboubker, Lotfi, Mateos, Maria-Victoria, Bahlis, Nizar, Popat, Rakesh, Besemer, Britta, Martínez-López, Joaquín, Sidana, Surbhi, Delforge, Michel, Pei, Lixia, Trancucci, Danielle, Verona, Raluca, Girgis, Suzette, Lin, Shun XW, Olyslager, Yunsi, Jaffe, Mindy, Uhlar, Clarissa, Stephenson, Tara, Van Rampelbergh, Rian, Banerjee, Arnob, Goldberg, Jenna D, Kobos, Rachel, Krishnan, Amrita, and Usmani, Saad Z
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Oncology and Carcinogenesis ,Cancer ,Clinical Research ,Vaccine Related ,Clinical Trials and Supportive Activities ,Biotechnology ,Rare Diseases ,Hematology ,6.2 Cellular and gene therapies ,Evaluation of treatments and therapeutic interventions ,Antibodies ,Bispecific ,Antibodies ,Monoclonal ,Humanized ,Antineoplastic Agents ,Antineoplastic Agents ,Immunological ,Antineoplastic Combined Chemotherapy Protocols ,B-Cell Maturation Antigen ,CD3 Complex ,Humans ,Injections ,Subcutaneous ,Multiple Myeloma ,Neoplasm Recurrence ,Local ,Recurrence ,T-Lymphocytes ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundTeclistamab 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.MethodsIn 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).ResultsAmong 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).ConclusionsTeclistamab 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.).
- Published
- 2022