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Cellular Dynamics Following CAR T Cell Therapy Are Associated with Response, Resistance and Cytokine Release Syndrome in Relapsed/Refractory Multiple Myeloma

Introduction The introduction of B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). While long-term follow-up of CD19 CAR T cells demonstrated a connection between CAR T cell expansion and pe...

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Bibliographic Details
Published in:Blood 2023-11, Vol.142 (Supplement 1), p.1008-1008
Main Authors: Fischer, Luise, Born, Patrick, Weiss, Ronald, Grieb, Nora, Seiffert, Sabine, Boldt, Andreas, Fricke, Stephan, Franz, Paul, Kloetzer, Christina, Heyn, Simone, Baber, Ronny, Wang, Song-Yau, Bach, Enrica, Hoffmann, Sandra, Ussmann, Jule, Kirchberg, Janine, Metzeler, Klaus H, Herling, Marco, Jentzsch, Madlen, Franke, Georg-Nikolaus, Sack, Ulrich, Reiche, Kristin, Koehl, Ulrike, Platzbecker, Uwe, Vucinic, Vladan, Merz, Maximilian
Format: Article
Language:English
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Summary:Introduction The introduction of B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). While long-term follow-up of CD19 CAR T cells demonstrated a connection between CAR T cell expansion and persistence with outcome, very little is known about persistence and effects on bystander cells of BCMA-targeting CAR T cells. Methods We analyzed 27 RRMM patients (pts) treated with Idecabtagene vicleucel (Ide-cel) at our center. Pts were grouped based on their remission evaluated 100 days after infusion into responders (partial response or better, n=16) or non-responders (progressive disease, n=11). Peripheral blood (pb) was drawn at day of leukapheresis, at day of infusion/after lymphodepletion (LD, d0) and at several time points following Ide-cel infusion (d7, d14, d30 and d100). In order to reflect a comprehensive picture of the longitudinal dynamics of CAR and non-CAR T cells, we subjected pb mononuclear cells to advanced flow cytometry. Additionally, we assessed the impact of cellular dynamics on the occurrence of cytokine release syndrome (CRS), tocilizumab application and the incidence of cytopenia. Results The median number of infused CAR T cells was 430x10 6 (range: 248.8 - 489.1x10 6) with one exception (25.7x10 6). There was no correlation between the median number of infused cells and in vivo expansion of CAR T cells after infusion as well as response or the development of CRS or cytopenia. Significant differences between responders and non-responders were already detected on day of leukapheresis: While non-responders showed similar numbers of CD4+ and CD8+ T cells, responders had significantly higher CD8+ T cell counts as compared to CD4+ T cells (p
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2023-188367