Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells. Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia. Our results show that in vivo expansion of CD8+ CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients. In addition, our data provide evidence, that an increased fraction of CD8+ T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome. We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion. Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented. [Figure not available: see fulltext.]
Details
Original language | English |
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Pages (from-to) | 372-382 |
Number of pages | 11 |
Journal | Leukemia |
Volume | 38 |
Issue number | 2 |
Publication status | Published - Feb 2024 |
Peer-reviewed | Yes |
External IDs
PubMed | 38184754 |
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ORCID | /0009-0001-6045-3349/work/153110097 |
Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- CD8-Positive T-Lymphocytes, Cytokine Release Syndrome, B-Cell Maturation Antigen, Humans, Immunotherapy, Adoptive/adverse effects, Multiple Myeloma/drug therapy