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

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

2024 | 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. Metzler, Marco Herling, Madlen Jentzsch, Georg-Nikolaus Franke, Ulrich Sack, Kristin Reiche, Ulrike Köhl, Uwe Platzbecker, Vladan Vucinic, Maximilian Merz
A comprehensive flow cytometry analysis of 27 patients with relapsed/refractory multiple myeloma (RRMM) treated with Idecabtagene vicleucel (Ide-cel) revealed that CD8⁺ CAR T cells expand in vivo and correlate with treatment response, while persistence is not essential for durable remission. The study found that a higher proportion of CD8⁺ T cells at leukapheresis, combined with successful lymphodepletion, positively influences treatment outcomes. Patients at risk for severe cytokine release syndrome (CRS) could be identified before lymphodepletion. The study also showed that CAR T cells affect bystander T cells, with CD8⁺ CAR T cells dominating the compartment. CAR T cell expansion was associated with CRS, and higher-grade CRS was linked to increased CD3⁺ T cells. Patients with CRS and tocilizumab treatment had higher CRP levels. The study highlights the importance of pre-treatment T cell composition and lymphodepletion in predicting treatment outcomes. CAR T cell therapy was associated with cytokine release syndrome and prolonged cytopenia, but these were not linked to treatment response. The study suggests that CAR T cell expansion is not essential for durable remission, and that the persistence of CAR T cells in peripheral blood is not critical. The study also shows that responders and non-responders can be distinguished by differences in CAR and non-CAR T cell composition at leukapheresis. The findings contribute to a better understanding of BCMA-targeting CAR T cell dynamics and their effects on treatment response and side effects. The study was supported by grants from the Deutsche Forschungsgemeinschaft and other organizations. The authors declare competing interests.A comprehensive flow cytometry analysis of 27 patients with relapsed/refractory multiple myeloma (RRMM) treated with Idecabtagene vicleucel (Ide-cel) revealed that CD8⁺ CAR T cells expand in vivo and correlate with treatment response, while persistence is not essential for durable remission. The study found that a higher proportion of CD8⁺ T cells at leukapheresis, combined with successful lymphodepletion, positively influences treatment outcomes. Patients at risk for severe cytokine release syndrome (CRS) could be identified before lymphodepletion. The study also showed that CAR T cells affect bystander T cells, with CD8⁺ CAR T cells dominating the compartment. CAR T cell expansion was associated with CRS, and higher-grade CRS was linked to increased CD3⁺ T cells. Patients with CRS and tocilizumab treatment had higher CRP levels. The study highlights the importance of pre-treatment T cell composition and lymphodepletion in predicting treatment outcomes. CAR T cell therapy was associated with cytokine release syndrome and prolonged cytopenia, but these were not linked to treatment response. The study suggests that CAR T cell expansion is not essential for durable remission, and that the persistence of CAR T cells in peripheral blood is not critical. The study also shows that responders and non-responders can be distinguished by differences in CAR and non-CAR T cell composition at leukapheresis. The findings contribute to a better understanding of BCMA-targeting CAR T cell dynamics and their effects on treatment response and side effects. The study was supported by grants from the Deutsche Forschungsgemeinschaft and other organizations. The authors declare competing interests.
Reach us at info@study.space
Understanding Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed%2Frefractory myeloma