In a phase I trial, the optimal dose of teclistamab produced an overall response rate of 65%.

  • Major Finding: In a phase I trial, the optimal dose of teclistamab produced an overall response rate of 65%.

  • Concept: Subcutaneous administration of this bispecific antibody may have reduced dose-limiting toxicities.

  • Impact: This study defines the recommended dose for phase II trials of teclistamab, which are now under way.

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B-cell maturation antigen (BCMA) is a validated target in multiple myeloma, with BCMA-directed chimeric antigen receptor T cells, bispecific antibodies, and antibody–drug conjugates all showing promise. Among these treatments is the T cell–redirecting bispecific IgG4 antibody teclistamab, which targets multiple myeloma cell BCMA and T cell CD3, but only preclinical results have been available for this agent. To assess teclistamab's clinical utility, Usmani and colleagues conducted a phase I, first-in-human trial enrolling 157 patients with relapsed or refractory multiple myeloma. Among these patients, 84 received teclistamab intravenously, while the remaining 73 patients received subcutaneous teclistamab, which was tested based on the possibility that it may be more convenient and perhaps cause fewer adverse events. Two dose-limiting toxicities—grade 4 delirium and grade 4 thrombocytopenia linked to cytokine release syndrome—occurred in patients receiving intravenous teclistamab, whereas no dose-limiting toxicities occurred in patients receiving subcutaneous teclistamab. Overall, 100% of patients experienced at least one treatment-emergent adverse event, with hematologic abnormalities and cytokine release syndrome predominating; however, none of the 40 patients receiving the recommended phase II dose (administered subcutaneously) discontinued treatment due to adverse events. Among patients who received the recommended phase II dose, the overall response rate was 65%, with 7 patients (18%) experiencing stringent complete responses (a normal free-light chain ratio plus the absence of clonal plasma cells in the bone marrow by immunohistochemistry), and the median duration of response was not reached after a median follow-up period of 6.1 months. In summary, this study demonstrates that teclistamab is clinically active in multiple myeloma and establishes the appropriate dose for a phase II trial, which is now under way.

Usmani SZ, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet 2021 Aug 10;398:665–74.

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