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Insight into mechanisms associated with cytokine release syndrome and neurotoxicity after CD19 CAR-T cell immunotherapy

Bone Marrow Transplantation volume 54, pages 780–784 (2019)Cite this article

Abstract

Adoptive immunotherapy with CD19-targeted chimeric antigen receptor (CAR)-T cells has been successful in producing durable remissions in some patients with relapsed or refractory B cell malignancies. Despite the efficacy of CAR-T cell therapy, significant toxicities can occur. Cytokine release syndrome (CRS) and neurotoxicity are the most common toxicities and can range from self-limited fever to life threatening organ damage and death. Understanding the mechanisms underlying these toxicities can help guide and improve outcomes. In this review we describe CRS and neurotoxicity in patients with B cell malignancies treated with CD19 CAR-T cells in pivotal trials, and also provide insight into potential mechanisms associated with these toxicities based on studies conducted in a phase 1/2 clinical trial at the Fred Hutchinson Cancer Research Center.

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Acknowledgements

We thank the FHCRC Cell Processing Facility and Seattle Cancer Care Alliance (SCCA) Cell Therapy Laboratory, and the staff of the Program in Immunology and SCCA Immunotherapy Clinic.

Funding

Funding for this work was provided by: Bezos Family Foundation. Publication of this supplement was sponsored by Gilead Sciences Europe Ltd, Cell Source, Inc., The Chorafas Institute for Scientific Exchange of the Weizmann Institute of Science, Kiadis Pharma, Miltenyi Biotec, Celgene, Centro Servizi Congressuali, Almog Diagnostic.

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Authors and Affiliations

  1. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Cassie K. Chou

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Cassie K. Chou & Cameron J. Turtle

  3. Department of Medicine, University of Washington, Seattle, WA, USA

    Cameron J. Turtle

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  1. Cassie K. Chou
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Correspondence to Cassie K. Chou.

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Conflict of interest

CKC declared no competing interests. CJT received consulting fees from Juno Therapeutics, Celgene, Nektar Therapeutics, Precision Biosciences, Eureka Therapeutics, Caribou Biosciences, Gilead, Bluebird, Adaptive Biotechnologies, Aptevo, research funding from Juno Therapeutics, Celgene, Nektar Therapeutics and holds patents licensed to cover technology related to cellular therapies with Juno/Celgene.

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Chou, C.K., Turtle, C.J. Insight into mechanisms associated with cytokine release syndrome and neurotoxicity after CD19 CAR-T cell immunotherapy. Bone Marrow Transplant 54 (Suppl 2), 780–784 (2019). https://doi.org/10.1038/s41409-019-0602-5

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