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Vol. 46. Issue 4.
Pages 201-212 (April 2022)
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Vol. 46. Issue 4.
Pages 201-212 (April 2022)
Review article
Immune effector cell-associated neurotoxicity syndrome: A therapeutic approach in the critically ill
Síndrome de neurotoxicidad asociada a células inmunoefectoras: un enfoque terapéutico en el paciente crítico
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J.C. Suarez Monteroa,
Corresponding author
JSuarez@santpau.cat

Corresponding author.
, A.C. Caballero Gonzalezb, L. Martín Aguilarc, J. Mancebo Cortésa
a Servicio de Medicina Intensiva, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
b Servicio de Hematología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
c Servicio de Neurología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
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Figures (2)
Tables (4)
Table 1. Incidence and clinical characteristics of neurotoxicity due to T-CAR cell therapy.
Table 2. Differential diagnosis of ICANS.
Table 3. Encephalopathy associated with immune-effector cells (ICE score).
Table 4. Levels of ICANS severity based on the ASBMT expert consensus.
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Abstract

Immunotherapy with chimeric antigen-specific receptor modified T cells, known as CAR-T, is emerging as a promising approach to hematological malignancies. In this regard, CAR-T against human cluster of differentiation (CD) 19 has demonstrated antitumor efficacy in application to B cell neoplasms resistant to conventional therapy. However, activation of the immune system induces severe and specific complications which can prove life-threatening. These include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (known as ICANS) - the latter being the subject of the present review. Although the physiopathological mechanisms underlying ICANS are not well known, a number of clinical and biological factors increase the risk of developing neurotoxicity associated to CAR-T therapy. Treatment is based on close monitoring, measures of support, anticonvulsivants, corticosteroids, and early admission to intensive care. The present study offers a comprehensive review of the available literature from a multidisciplinary perspective, including recommendations from intensivists, neurologists and hematologists dedicated to the care of critically ill adults.

Keywords:
Chimeric antigen receptor T-cell therapy
Immune effector cell-associated neurotoxicity syndrome
Critically ill
Resumen

La inmunoterapia con células T modificadas con receptor quimérico antígeno-específico (chimeric antigen receptor conocida como [CAR-T]) está emergiendo como un tratamiento prometedor para enfermedades hematológicas. Así, las CAR-T dirigidas contra el complejo de diferenciación (CD) 19 han demostrado gran eficacia antitumoral contra neoplasias de células B resistentes a terapias convencionales. Sin embargo, la activación dirigida de la respuesta inmunitaria desata en ciertos casos complicaciones específicas graves y potencialmente mortales. Entre ellas cabe destacar el síndrome de liberación de citoquinas y el síndrome de toxicidad neurológica asociado a la terapia con células inmuno-efectoras (Immune-effector cell associated neurotoxicity syndrome conocido como ICANS) siendo este último el objetivo de nuestra revisión. Aunque los mecanismos fisiopatológicos que conducen al ICANS son poco conocidos, existen factores clínicos y biológicos que aumentan el riesgo de desarrollo de neurotoxicidad asociada a terapia CAR-T. El tratamiento se basa en medidas de monitorización y soporte, tratamiento con anticonvulsivantes, corticosteroides e ingreso en los Servicios de Medicina Intensiva de forma precoz. Este artículo proporciona una revisión exhaustiva de la literatura disponible sobre el ICANS desde una perspectiva multidisciplinar, incluyendo recomendaciones de intensivistas, neurólogos y hematólogos formados en el cuidado de adultos críticamente enfermos.

Palabras clave:
Terapia de células T con receptores quiméricos de antígenos
Síndrome de neurotoxicidad asociada a células inmunoefectoras
Paciente crítico

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