EASIX and Severe Endothelial Complications After CD19-Directed CAR-T Cell Therapy-A Cohort Study.
CAR-T cell
CRS
EASIX
ICANS
prognostic biomarker
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
16
02
2022
accepted:
10
03
2022
entrez:
25
4
2022
pubmed:
26
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
Endothelial dysfunction is associated with two main complications of chimeric antigen receptor T (CAR-T) cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This study evaluates the Endothelial Activation and Stress Index (EASIX) as a prognostic marker for high-grade CRS and ICANS in patients treated with CD19-directed CAR-T cells. In this retrospective study, a training cohort of 93 patients from the ZUMA-1 trial and a validation cohort of 121 patients from two independent centers (University Hospital Heidelberg, Charité University Medicine Berlin) were investigated. The primary objective was to assess the predictive capacity of EASIX measured immediately before the start of lymphodepletion (EASIX-pre) for the occurrence of grade ≥3 CRS and/or ICANS. To explore a possible endothelial link, serum levels of endothelial stress markers (angiopoietin-2, suppressor of tumorigenicity-2, soluble thrombomodulin, and interleukin-8) were determined before lymphodepletion and on day 7 after CART infusion in the validation cohort ( The prognostic effect of EASIX-pre on grade ≥3 CRS and/or ICANS was significant in the training cohort [OR 2-fold increase 1.72 (1.26-2.46)] and validated in the independent cohort. An EASIX-pre cutoff >4.67 derived from the training cohort associated with a 4.3-fold increased odds ratio of severe CRS/ICANS in the independent cohort. Serum endothelial distress markers measured on day+7 correlated with EASIX-pre and associated with severe complications. EASIX-pre is a powerful predictor of severe CRS/ICANS after CD19-directed CART therapy and might be used as a basis for risk-adapted prevention strategies.
Sections du résumé
Background
Endothelial dysfunction is associated with two main complications of chimeric antigen receptor T (CAR-T) cell therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). This study evaluates the Endothelial Activation and Stress Index (EASIX) as a prognostic marker for high-grade CRS and ICANS in patients treated with CD19-directed CAR-T cells.
Methods
In this retrospective study, a training cohort of 93 patients from the ZUMA-1 trial and a validation cohort of 121 patients from two independent centers (University Hospital Heidelberg, Charité University Medicine Berlin) were investigated. The primary objective was to assess the predictive capacity of EASIX measured immediately before the start of lymphodepletion (EASIX-pre) for the occurrence of grade ≥3 CRS and/or ICANS. To explore a possible endothelial link, serum levels of endothelial stress markers (angiopoietin-2, suppressor of tumorigenicity-2, soluble thrombomodulin, and interleukin-8) were determined before lymphodepletion and on day 7 after CART infusion in the validation cohort (
Results
The prognostic effect of EASIX-pre on grade ≥3 CRS and/or ICANS was significant in the training cohort [OR 2-fold increase 1.72 (1.26-2.46)] and validated in the independent cohort. An EASIX-pre cutoff >4.67 derived from the training cohort associated with a 4.3-fold increased odds ratio of severe CRS/ICANS in the independent cohort. Serum endothelial distress markers measured on day+7 correlated with EASIX-pre and associated with severe complications.
Conclusions
EASIX-pre is a powerful predictor of severe CRS/ICANS after CD19-directed CART therapy and might be used as a basis for risk-adapted prevention strategies.
Identifiants
pubmed: 35464403
doi: 10.3389/fimmu.2022.877477
pmc: PMC9033201
doi:
Substances chimiques
Antigens, CD19
0
Biomarkers
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
877477Informations de copyright
Copyright © 2022 Korell, Penack, Mattie, Schreck, Benner, Krzykalla, Wang, Schmitt, Bullinger, Müller-Tidow, Dreger and Luft.
Déclaration de conflit d'intérêts
Authors MM and ZW were employed by the company Kite Pharma, Gilead. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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