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Der kritisch kranke Patient nach CAR-T-Zell-Therapie

Relevante Nebenwirkungen, deren Management und Herausforderungen an die Intensivmedizin

The critically ill CAR T-cell patient

Relevant toxicities, their management and challenges in critical care

  • Intensivmedizin
  • Published:
Wiener klinisches Magazin Aims and scope

Zusammenfassung

Hintergrund

Die Therapie mit Chimeric-antigen-receptor(CAR)-T-Zellen hat sich als neue Therapieform in der Onkologie etabliert. Im Rahmen einer Therapie mit CAR-T-Zellen kommt es regelhaft zu schweren Nebenwirkungen.

Material und Methoden

Review der Literatur zu CAR-T-Zell-Therapie, Toxizitäten und Nebenwirkungsmanagement

Ergebnis

Das „cytokine release syndrome“ (CRS) und das „immune effector cell-associated neurotoxicity syndrome“ (ICANS) treten regelhaft im Rahmen einer Therapie mit CAR-T-Zellen auf. Das CRS kann von einer milden grippeähnlichen Symptomatik bis hin zu einem Multiorganversagen führen. Bei ICANS kann sich letztendlich ein lebensbedrohliches Hirnödem entwickeln. Bei der Pathophysiologie des CRS spielt insbesondere das Interleukin‑6 eine entscheidende Rolle. Die Pathophysiologie des ICANS ist nicht vollständig verstanden. Das Management richtet sich nach dem Schweregrad gemäß Grading der American Society for Transplantation and Cellular Therapy (ASTCT). Beim CRS werden Tocilizumab und Kortikosteroide, für das ICANS Kortikosteroide empfohlen.

Diskussion

Nach einer CAR-T-Zell-Therapie kommt es regelhaft zu potenziell lebensbedrohlichen Komplikationen. Weitergehende Therapieansätze sind bislang nicht gut untersucht. Eine interdisziplinäre Zusammenarbeit zwischen Intensivmediziner*innen, Hämatolog*innen, Neurolog*innen und Ärzt*innen anderer Fachabteilungen ist von entscheidender Bedeutung. Aufgrund der steigenden Patientenzahlen ist von einer Zunahme an Patienten mit Notwendigkeit einer intensivmedizinischen Behandlung im Rahmen einer CAR-T-Zelltherapie auszugehen.

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.

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Authors and Affiliations

  1. Klinik I für Innere Medizin, Schwerpunkt Internistische Intensivmedizin, Klinikum der Universität Köln, Kerpener Str. 62, 50937, Köln, Deutschland

    Jorge Garcia Borrega,  Katrin Heindel,  Matthias Kochanek &  Boris Böll

  2. Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf (CIO ABCD), Köln, Deutschland

    Jorge Garcia Borrega,  Katrin Heindel,  Matthias Kochanek &  Boris Böll

  3. Klinik für Neurologie, Klinikum der Universität Köln, Köln, Deutschland

    Clemens Warnke

  4. Medizinische Klinik und Poliklinik III, Klinikum der Ludwig-Maximilians-Universität München, München, Deutschland

    Joachim Stemmler &  Michael von Bergwelt-Baildon

  5. Klinik für Innere Medizin V, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    Tobias Liebregts

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  1. Jorge Garcia Borrega
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Correspondence to Boris Böll.

Ethics declarations

Interessenkonflikt

J. Garcia Borrega hat Reisekosten und Kongressgebühren von Kite/Gilead erhalten. M. Kochanek hat Honorare von Astellas, Gilead, MSD und Pfizer erhalten. M. von Bergwelt-Baildon erhielt Forschungsmittel und Honorare von Novartis, Kite/Gilead, Miltenyi und Roche. B. Böll hat Forschungsmittel und Honorare von Novartis, Kite/Gilead, Miltenyi, Roche und Janssen & Janssen erhalten. K. Heindel, C. Warnke, J. Stemmler und T. Liebregts geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

M. Kochanek, M. von Bergwelt-Baildon, T. Liebregts und B. Böll beteiligen sich an der Initiative Intensive Care in Hematologic and Oncologic Patients (iCHOP).

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Garcia Borrega, J., Heindel, K., Kochanek, M. et al. Der kritisch kranke Patient nach CAR-T-Zell-Therapie. Wien klin Mag 24, 196–203 (2021). https://doi.org/10.1007/s00740-021-00416-x

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