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Review
. 2020 Jun;20(6):653-664.
doi: 10.1080/14712598.2020.1729735. Epub 2020 Feb 24.

Assessment and management of cytokine release syndrome and neurotoxicity following CD19 CAR-T cell therapy

Cassie K Chou  1   2 , Cameron J Turtle  1   3
Affiliations
Review

Assessment and management of cytokine release syndrome and neurotoxicity following CD19 CAR-T cell therapy

Cassie K Chou et al. Expert Opin Biol Ther. 2020 Jun.

Abstract

Introduction: The success of CD19 chimeric antigen receptor (CAR)-T cell therapy for treatment of CD19 positive malignancies has led to the FDA approval of two CD19 CAR-T cell products, tisagenlecleucel and axicabtagene ciloleucel, and ongoing clinical trials of new products. Cytokine release syndrome (CRS) and neurotoxicity are common toxicities associated with CD19 CAR-T cell therapies.Areas covered: This review will discuss CRS and neurotoxicity associated with CD19 CAR-T cell therapies, including clinical presentation, risk factors, pathophysiology, and therapeutic or prophylactic interventions.Expert opinion: In conjunction with improved understanding of the pathophysiology of CRS and neurotoxicity, we expect that the recent development of consensus guidelines for the evaluation of these toxicities will enhance management of patients undergoing CD19 CAR-T cell therapies.

Keywords: CAR-T cell; CD19 malignancies; chimeric antigen receptor; cytokine release syndrome; immunotherapy; leukemia; lymphoma; neurotoxicity.

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Conflict of interest statement

Declaration of Interests

CJ Turtle has received research funding from Juno/BMS, Nektar Therapeutics; is on scientific advisory boards for Precision Biosciences, T-CURX, Eureka Therapeutics, Caribou Biosciences, Myeloid Therapeutics, Arsenal Bio; has equity in Precision Biosciences, Eureka Therapeutics, Caribou Bioscience, Myeloid Therapeutics, Arsenal Bio; acted ad hoc on advisory boards (last 12 months) for , Kite/Gilead, , Allogene, PACT Pharma, Nektar Therapeutics, Astra Zeneca; and has patents pending to cover technology related to cellular therapies with Juno/BMS. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1:
Figure 1:
Brain MRI images from patients with severe neurotoxicity following CD19 CAR-T cell therapy. A, Symmetric edema of deep structures (arrowheads). B, Global cerebral edema with blurring of gray-white junction (stars) and slit-like ventricles (arrowhead). C, Diffuse leptomeningeal enhancement (arrowheads). D, focal white matter hyperintensities (arrowheads). (Modified and reprinted from [49])
See this image and copyright information in PMC

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