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EASIX and severe endothelial complications after CD19-directed CAR-T Cell therapy-a cohort study

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Item Type:Article
Title:EASIX and severe endothelial complications after CD19-directed CAR-T Cell therapy-a cohort study
Creators Name:Korell, F., Penack, O., Mattie, M., Schreck, N., Benner, A., Krzykalla, J., Wang, Z., Schmitt, M., Bullinger, L., Müller-Tidow, C., Dreger, P. and Luft, T.
Abstract: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 (n = 47). 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.
Keywords:CAR-T Cell, EASIX, CRS, ICANS, Prognostic Biomarker
Source:Frontiers in Immunology
ISSN:1664-3224
Publisher:Frontiers Media SA
Volume:13
Page Range:877477
Date:8 April 2022
Official Publication:https://doi.org/10.3389/fimmu.2022.877477
PubMed:View item in PubMed

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