CD8 effector T cells enhance response in BCMA-exposed and -naïve multiple myeloma.

Teclistamab, a B-cell maturation antigen (BCMA)- and CD3-targeting bispecific antibody, is an effective novel treatment for relapsed/refractory multiple myeloma (RRMM), but efficacy in BCMA-exposed patients and mechanisms of resistance have yet to be fully delineated. We conducted a real-world retrospective study of commercial teclistamab, capturing both clinical outcomes and immune correlates of treatment response in a cohort of patients (n = 52) with advanced RRMM. Teclistamab was highly effective with an overall response rate (ORR) of 64%, including an ORR of 50% for patients with prior anti-BCMA therapy. Pre-treatment plasma cell BCMA expression levels had no bearing on response. However, comprehensive pre-treatment immune profiling identified that effector CD8+ T cell populations associated with response to therapy and a regulatory T cell population associated with non-response, indicating a contribution of immune status in outcomes with potential utility as a biomarker signature to guide patient management.