Journal Article

DKFZ-2023-01923

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.DKFZ* ; Bücklein, V. L.DKFZ* ; Völkl, S. ; Penack, O. ; Albanyan, O. ; Stock, S.DKFZ* ; Müller, F. ; Karschnia, P. ; Petrera, A. ; Reid, K. ; Faramand, R. ; Davila, M. L. ; Modi, K. ; Dean, E. A. ; Bachmeier, C. ; von Bergwelt-Baildon, M.DKFZ* ; Locke, F. L. ; Bethge, W. ; Bullinger, L.DKFZ* ; Mackensen, A. ; Barba, P. ; Jain, M. D. ; Subklewe, M.DKFZ*

2023
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.adg3919

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.

Keyword(s): Humans (MeSH) ; Immunotherapy, Adoptive: adverse effects (MeSH) ; Receptors, Chimeric Antigen (MeSH) ; Adaptor Proteins, Signal Transducing (MeSH) ; Antigens, CD19 (MeSH) ; Cell Cycle (MeSH) ; Receptors, Chimeric Antigen ; Adaptor Proteins, Signal Transducing ; Antigens, CD19

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)
2. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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