Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Luise Fischer - , Leipzig University (Author)
  • Nora Grieb - , Leipzig University, Innovation Center Computer Assisted Surgery (ICCAS) (Author)
  • Patrick Born - , Leipzig University (Author)
  • Ronald Weiss - , Leipzig University, Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Sabine Seiffert - , Leipzig University (Author)
  • Andreas Boldt - , Leipzig University (Author)
  • Stephan Fricke - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Paul Franz - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Simone Heyn - , Leipzig University (Author)
  • Anne Sophie Kubasch - , Leipzig University (Author)
  • Ronny Baber - , Leipzig University (Author)
  • Heike Weidner - , Department of internal Medicine 3, University Hospital Carl Gustav Carus Dresden (Author)
  • Song Yau Wang - , Leipzig University (Author)
  • Enrica Bach - , Leipzig University (Author)
  • Sandra Hoffmann - , Leipzig University (Author)
  • Jule Ussmann - , Leipzig University (Author)
  • Janine Kirchberg - , Leipzig University (Author)
  • Saskia Hell - , Leipzig University (Author)
  • Sebastian Schwind - , Leipzig University (Author)
  • Klaus H. Metzeler - , Leipzig University (Author)
  • Marco Herling - , Leipzig University (Author)
  • Madlen Jentzsch - , Leipzig University (Author)
  • Georg Nikolaus Franke - , Leipzig University (Author)
  • Ulrich Sack - , Leipzig University (Author)
  • Kristin Reiche - , Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Ulrike Köhl - , Leipzig University, Fraunhofer Institute for Cell Therapy and Immunology (Author)
  • Uwe Platzbecker - , Leipzig University (Author)
  • Vladan Vucinic - , Leipzig University (Author)
  • Maximilian Merz - , Leipzig University (Author)

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 languageEnglish
Pages (from-to)372-382
Number of pages11
JournalLeukemia
Volume38
Issue number2
Publication statusPublished - Feb 2024
Peer-reviewedYes

External IDs

PubMed 38184754
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