Efficacy and safety of teclistamab in triple‐class exposed relapsed/refractory multiple myeloma: Pooled findings from three clinical cohorts and a retrospective cohort

Abstract Background Teclistamab is the first approved bispecific antibody targeting B‐cell maturation antigen. It has demonstrated rapid, deep, durable responses with manageable safety in patients with triple‐class exposed relapsed/refractory multiple myeloma (TCE RRMM). Methods The authors report results from three cohorts: Global Trial cohort consisting of 217 patients from three registrational studies (pivotal MajesTEC‐1 study [ n = 165], China cohort of MajesTEC‐1 [ n = 26], and the Japan MMY1002 study [ n = 26]); the subset of 52 of 217 patients formed the Asian Trial cohort, and 42 patients treated outside of trials in the pre‐approval access (PAA) program formed the Asian PAA cohort. Results In the Global Trial cohort, median age was 65 years, weight was 69 kg, and prior lines‐of‐therapy was five; 29.0% had high‐risk cytogenetics and 18.9% had extramedullary disease. With 29.5 months median follow‐up, overall response rate (ORR)/≥complete response (CR) was 66.4%/50.2%, median duration of response (DOR) was not reached; progression‐free survival (PFS) and overall survival (OS) were 15.6, and 29.1 months, respectively. In the subset of Asian Trial cohort, baseline features were similar except for lower weight (median, 58 kg); median follow‐up was 26.3 months. ORR/≥CR was 76.9%/63.5%, 24‐month DOR, PFS, and OS rates were 67.5%, 59.5%, 71.4%, respectively, with medians not yet reached. Efficacy was consistent in the Asian PAA cohort with ORR/≥CR of 66.7%/40.5%. Most common adverse events were cytopenias, cytokine release syndrome, and infections. Infection management improved over time, supported by increased immunoglobulin use in later‐enrolling Asian studies, aligned with guideline adoption. Conclusion Teclistamab demonstrated clinically meaningful benefits across diverse patients, encompassing various weight categories and geographies, reinforcing its potential as a standard of care for TCE RRMM. Trial Registration ClinicalTrials.gov MajesTEC‐1 (NCT03145181 and NCT04557098) and Japan MMY1002 study (NCT04696809)