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

Blood Adv. 2024 Apr 9;8(7):1600-1611. doi: 10.1182/bloodadvances.2023011225.

Abstract

Teclistamab, a B-cell maturation antigen (BCMA)- and CD3-targeting bispecific antibody, is an effective novel treatment for relapsed/refractory multiple myeloma (R/RMM), but efficacy in patients exposed to BCMA-directed therapies 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 R/RMM. Teclistamab was highly effective with an overall response rate (ORR) of 64%, including an ORR of 50% for patients with prior anti-BCMA therapy. Pretreatment plasma cell BCMA expression levels had no bearing on response. However, comprehensive pretreatment immune profiling identified that effector CD8+ T-cell populations were associated with response to therapy and a regulatory T-cell population associated with nonresponse, indicating a contribution of immune status in outcomes with potential utility as a biomarker signature to guide patient management.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • B-Cell Maturation Antigen / therapeutic use
  • CD8-Positive T-Lymphocytes / metabolism
  • Humans
  • Multiple Myeloma* / drug therapy
  • Retrospective Studies

Substances

  • B-Cell Maturation Antigen
  • Antineoplastic Agents