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How I treat refractory CRS and ICANS after CAR T-cell therapy

The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and im...

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Autores principales: Jain, Michael D., Smith, Melody, Shah, Nirali N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329191/
https://www.ncbi.nlm.nih.gov/pubmed/36989488
http://dx.doi.org/10.1182/blood.2022017414
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author Jain, Michael D.
Smith, Melody
Shah, Nirali N.
author_facet Jain, Michael D.
Smith, Melody
Shah, Nirali N.
author_sort Jain, Michael D.
collection PubMed
description The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities.
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spelling pubmed-103291912023-07-09 How I treat refractory CRS and ICANS after CAR T-cell therapy Jain, Michael D. Smith, Melody Shah, Nirali N. Blood Emergent Car T-Cell Toxicities The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities. The American Society of Hematology 2023-05-18 2023-03-31 /pmc/articles/PMC10329191/ /pubmed/36989488 http://dx.doi.org/10.1182/blood.2022017414 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Emergent Car T-Cell Toxicities
Jain, Michael D.
Smith, Melody
Shah, Nirali N.
How I treat refractory CRS and ICANS after CAR T-cell therapy
title How I treat refractory CRS and ICANS after CAR T-cell therapy
title_full How I treat refractory CRS and ICANS after CAR T-cell therapy
title_fullStr How I treat refractory CRS and ICANS after CAR T-cell therapy
title_full_unstemmed How I treat refractory CRS and ICANS after CAR T-cell therapy
title_short How I treat refractory CRS and ICANS after CAR T-cell therapy
title_sort how i treat refractory crs and icans after car t-cell therapy
topic Emergent Car T-Cell Toxicities
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10329191/
https://www.ncbi.nlm.nih.gov/pubmed/36989488
http://dx.doi.org/10.1182/blood.2022017414
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