Impact of prior BCMA-targeted therapy on CAR-T expansion and host T-cell phenotypes in patients with Relapsed/Refractory multiple myeloma receiving BCMA CAR-T therapy

作者：Kevin Reyes, Jodi Lipof, Serena S. Kwek, Averey Lea, Matthew Clark, Lisa Dunn, Ruixin Sun, Emily Mohler, Jane Greenaway, Darren Pan, Anupama Kumar, Alfred Chung, Peter H. Sayre, Shagun Arora, Jeffrey L. Wolf, Thomas R. Martin, Ajai Chari, David Y. Oh · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3916 · 研究领域：CAR-T cell therapy research、Multiple Myeloma Research and Treatments、Monoclonal and Polyclonal Antibodies Research

Abstract Background: B-cell maturation antigen (BCMA)-targeted therapies such as chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies have demonstrated therapeutic efficacy with robust response rates and improved survival in patients with relapsed/refractory multiple myeloma (RRMM). Prior exposure to BCMA-targeted therapies has been shown to negatively impact the efficacy of subsequent BCMA-directed CAR-T cell therapy and is associated with an altered immune landscape. However, the effect of prior exposure to BCMA-targeted therapy on CAR-T expansion, self-renewing host T cell phenotypes, and their association with therapeutic efficacy in patients with RRMM receiving BCMA CAR-T have yet to be characterized. Methods From cryopreserved peripheral blood mononuclear cells (PBMCs), we performed spectral flow cytometry with a ~40-plex panel on serial timepoints ranging from day -5 before BCMA-directed CAR-T infusion, up to month 12 post CAR-T infusion. BCMA-directed CAR were gated by staining with fluorophore-conjugated soluble BCMA antigen or a rabbit anti-camelid VHH antibody. Data was acquired on a Cytek Aurora. The BCMA CAR-Ts for RRMM were either ciltacabtagene autoleucel (ciltacel) given as standard of care, or through an investigator-initiated trial of a UCSF-manufactured BCMA-directed CAR-T for triple-class refractory MM (NCT05577000). Group 1 of collections included 10 RRMM patients receiving BCMA-directed CAR-T without prior BCMA-targeted therapy (ant...