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Cytokine release syndrome and neurotoxicity after CD 19 chimeric antigen receptor‐modified ( CAR ‐) T cell therapy
Author(s) -
Hay Kevin A.
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15644
Subject(s) - cytokine release syndrome , chimeric antigen receptor , medicine , neurotoxicity , immunology , cytokine , population , t cell , toxicity , pharmacology , immune system , environmental health
Summary Chimeric antigen receptor‐modified ( CAR )‐T cells have demonstrated impressive results in the treatment of haematological malignancies. However, cytokine release syndrome ( CRS ) and neurotoxicity are common toxicities which are potentially life‐threatening in severe cases. Risk factors for CRS and neurotoxicity identified so far include disease burden, lymphodepletion intensity and CAR ‐T cell dose administered. Risk‐adapted dosing, with lower CAR ‐T cell doses administered to B‐cell acute lymphoblastic leukaemia patients with high marrow blast counts, has been successful at decreasing severe CRS rates in this population. Intervention with therapies, such as tocilizumab and corticosteroids, have been effective at ameliorating toxicity, enabling CAR ‐T cells to be administered safely to many patients without significantly compromising efficacy. Deeper understanding of the pathophysiology of underlying CRS and neurotoxicity will enable the development of novel approaches to reduce toxicity and improve outcomes.