J Garcia Borrega1,2, K Heindel1,2, M Kochanek1,2, C Warnke3, J Stemmler4, M von Bergwelt-Baildon4, T Liebregts5, B Böll6,7. 1. Klinik I für Innere Medizin, Schwerpunkt Internistische Intensivmedizin, Klinikum der Universität Köln, Kerpener Str. 62, 50937, Köln, Deutschland. 2. Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO ABCD), Köln, Deutschland. 3. Klinik für Neurologie, Klinikum der Universität Köln, Köln, Deutschland. 4. Medizinische Klinik und Poliklinik III, Klinikum der Ludwig-Maximilians-Universität München, München, Deutschland. 5. Klinik für Innere Medizin V, Universitätsklinikum Heidelberg, Heidelberg, Deutschland. 6. Klinik I für Innere Medizin, Schwerpunkt Internistische Intensivmedizin, Klinikum der Universität Köln, Kerpener Str. 62, 50937, Köln, Deutschland. boris.boell@uk-koeln.de. 7. Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO ABCD), Köln, Deutschland. boris.boell@uk-koeln.de.
Abstract
BACKGROUND: CAR‑T cell therapy has been implemented as clinical routine treatment option during the last decade. Despite beneficial outcomes in many patients severe side effects and toxicities are seen regularly that can compromise the treatment success. METHODS: Literature review: CAR T‑cell therapy, toxicities and their management RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) are seen regularly after CAR T‑cell treatment. CRS symptoms can range from mild flu-like symptoms to severe organ dysfunction requiring vasopressor therapy, mechanical ventilation and other intensive care support. ICANS symptoms usually develop later and can range from disorientation and aphasia to potentially life-threatening brain edema. IL‑6 is a key factor in the pathophysiology of CRS. The pathophysiology of ICANS is not fully understood. The ASTCT consensus grading is recommended to stratify patients for different management options. An interdisciplinary team including hematologist, intensivist, neurologists and other specialties is needed to optimize the treatment. DISCUSSION: Severe and potentially life-threatening toxicities occur regularly after CAR T‑cell therapy. Treatment strategies for CRS and ICANS still need to be evaluated prospectively. Due to the increasing number of patients treated with CAR T‑cells the number of patients requiring temporary intensive care management due to CRS and ICANS is expected to increase during the next years.
BACKGROUND: CAR‑T cell therapy has been implemented as clinical routine treatment option during the last decade. Despite beneficial outcomes in many patients severe side effects and toxicities are seen regularly that can compromise the treatment success. METHODS: Literature review: CAR T‑cell therapy, toxicities and their management RESULTS: The cytokine release syndrome (CRS) and the immune effector cell-associated neurotoxicity syndrome (ICANS) are seen regularly after CAR T‑cell treatment. CRS symptoms can range from mild flu-like symptoms to severe organ dysfunction requiring vasopressor therapy, mechanical ventilation and other intensive care support. ICANS symptoms usually develop later and can range from disorientation and aphasia to potentially life-threatening brain edema. IL‑6 is a key factor in the pathophysiology of CRS. The pathophysiology of ICANS is not fully understood. The ASTCT consensus grading is recommended to stratify patients for different management options. An interdisciplinary team including hematologist, intensivist, neurologists and other specialties is needed to optimize the treatment. DISCUSSION: Severe and potentially life-threatening toxicities occur regularly after CAR T‑cell therapy. Treatment strategies for CRS and ICANS still need to be evaluated prospectively. Due to the increasing number of patients treated with CAR T‑cells the number of patients requiring temporary intensive care management due to CRS and ICANS is expected to increase during the next years.
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