Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion
Rejeski K, Perez A, Iacoboni G, Blumenberg V, Bücklein VL, Völkl S, Penack O, Albanyan O, Stock S, Müller F, Karschnia P, Petrera A, Reid K, Faramand R, Davila ML, Modi K, Dean EA, Bachmeier C, von Bergwelt-Baildon M, Locke FL, Bethge W, Bullinger L, Mackensen A, Barba P, Jain MD, Subklewe M (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 9
Pages Range: eadg3919-
Journal Issue: 38
Abstract
Prolonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with "intermittent" neutrophil recovery (e.g., recurrent neutrophil dips) compared to either "quick" or "aplastic" recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.
Involved external institutions
Klinikum der Universität München
Germany (DE)
H. Lee Moffitt Cancer Center & Research Institute
United States (USA) (US)
Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron
Spain (ES)
Bayerisches Zentrum für Krebsforschung (BZKF)
Germany (DE)
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
University of Florida
United States (USA) (US)
Universitätsklinikum Tübingen
Germany (DE)
Germany (DE)
H. Lee Moffitt Cancer Center & Research Institute
United States (USA) (US)
Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron
Spain (ES)
Bayerisches Zentrum für Krebsforschung (BZKF)
Germany (DE)
Deutsches Krebsforschungszentrum (DKFZ)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
University of Florida
United States (USA) (US)
Universitätsklinikum Tübingen
Germany (DE)
How to cite
APA:
Rejeski, K., Perez, A., Iacoboni, G., Blumenberg, V., Bücklein, V.L., Völkl, S.,... Subklewe, M. (2023). Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion. Science Advances, 9(38), eadg3919-. https://doi.org/10.1126/sciadv.adg3919
MLA:
Rejeski, Kai, et al. "Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion." Science Advances 9.38 (2023): eadg3919-.
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