%0 Journal Article %1 Fischer2024 %A Fischer, Luise %A Grieb, Nora %A Born, Patrick %A Weiss, Ronald %A Seiffert, Sabine %A Boldt, Andreas %A Fricke, Stephan %A Franz, Paul %A Heyn, Simone %A Kubasch, Anne Sophie %A Baber, Ronny %A Weidner, Heike %A Wang, Song Yau %A Bach, Enrica %A Hoffmann, Sandra %A Ussmann, Jule %A Kirchberg, Janine %A Hell, Saskia %A Schwind, Sebastian %A Metzeler, Klaus H. %A Herling, Marco %A Jentzsch, Madlen %A Franke, Georg-Nikolaus %A Sack, Ulrich %A Reiche, Kristin %A Köhl, Ulrike %A Platzbecker, Uwe %A Vucinic, Vladan %A Merz, Maximilian %D 2024 %J Leukemia %K imported from:scadsfct %N 2 %P 372--382 %R 10.1038/s41375-023-02129-y %T Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma %U https://doi.org/10.1038/s41375-023-02129-y %V 38 %X 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.

@article{Fischer2024, 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.}, added-at = {2024-12-18T14:15:23.000+0100}, author = {Fischer, Luise and Grieb, Nora and Born, Patrick and Weiss, Ronald and Seiffert, Sabine and Boldt, Andreas and Fricke, Stephan and Franz, Paul and Heyn, Simone and Kubasch, Anne Sophie and Baber, Ronny and Weidner, Heike and Wang, Song Yau and Bach, Enrica and Hoffmann, Sandra and Ussmann, Jule and Kirchberg, Janine and Hell, Saskia and Schwind, Sebastian and Metzeler, Klaus H. and Herling, Marco and Jentzsch, Madlen and Franke, Georg-Nikolaus and Sack, Ulrich and Reiche, Kristin and K{\"o}hl, Ulrike and Platzbecker, Uwe and Vucinic, Vladan and Merz, Maximilian}, biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/29108f833330e89ee4cfe8f4cf701df92/scads.ai}, day = 01, doi = {10.1038/s41375-023-02129-y}, interhash = {8f04d3efbfa880111d1763fb32fc9ad9}, intrahash = {9108f833330e89ee4cfe8f4cf701df92}, issn = {1476-5551}, journal = {Leukemia}, keywords = {imported from:scadsfct}, month = feb, number = 2, pages = {372--382}, timestamp = {2024-12-18T14:15:23.000+0100}, title = {Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma}, url = {https://doi.org/10.1038/s41375-023-02129-y}, volume = 38, year = 2024 }