Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma
Luise Fischer, Nora Grieb, Patrick Born, Ronald Weiss, Sabine Seiffert, Andreas Boldt, Stephan Fricke, Paul Franz, Simone Heyn, Anne Sophie Kubasch, Ronny Baber, Heike Weidner, Song‐Yau Wang, Enrica Bach, Sandra Hoffmann, Jule Ussmann, Janine Kirchberg, Saskia Hell, Sebastian Schwind, Klaus H. Metzeler, Marco Herling, Madlen Jentzsch, Georg‐Nikolaus Franke, Ulrich Sack, Kristin Reiche, Ulrike Köhl, Uwe Platzbecker, Vladan Vučinić, Maximilian Merz
Abstract
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.