Open AccessIn the Eye of the Storm: Immune‐mediated Toxicities Associated With CAR‐T Cell Therapy
Author(s) -
Garcia Borrega Jorge,
Gödel Philipp,
Rüger Maria Adele,
Onur Özgür A.,
ShimabukuroVornhagen Alexander,
Kochanek Matthias,
Böll Boris
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/hs9.0000000000000191
Subject(s) - chimeric antigen receptor , cytokine release syndrome , cytokine storm , immune system , medicine , neurotoxicity , immunotherapy , immunology , t cell , bioinformatics , biology , toxicity , disease , covid-19 , infectious disease (medical specialty)
The success of chimeric antigen receptor (CAR)‐T cell therapy with impressive response rates in hematologic malignancies but also promising data in solid tumors came along with the cognition of unexpected, potentially life‐threatening immune‐mediated toxicities, namely the cytokine release syndrome (CRS) and neurotoxicity recently referred to as “immune effector cell‐associated neurotoxicity syndrome” (ICANS). These toxicities require urgent diagnostic and therapeutic interventions and targeted modulation of key cytokine pathways represents the mainstay of CRS treatment. However, as the underlying mechanisms of ICANS are not well understood, treatment options remain limited and further investigation is warranted. Importantly, after the recent market approval of 2 CAR‐T cell constructs, the application of CAR‐T cells will expand to nonacademic centers with limited experience in the management of CAR‐T cell‐associated toxicities. Here, we review the current evidence of CRS and ICANS pathophysiology, diagnostics, and treatment.