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Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy

Authors Riegler LL, Jones GP, Lee DW

Received 22 July 2018

Accepted for publication 11 October 2018

Published 28 February 2019 Volume 2019:15 Pages 323—335

DOI https://doi.org/10.2147/TCRM.S150524

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Garry Walsh


Lara L Riegler,1 Gavin P Jones,2 Daniel W Lee1

1Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA; 2School of Medicine, University of Virginia, Charlottesville, VA, USA

Abstract: With immunotherapy innovations for cancer treatment, in particular chimeric antigen receptor (CAR) T cells, becoming more successful and prevalent, strategies to mitigate and manage their toxicities are required. Anti-CD19 CAR T-cell therapy has revolutionized the treatment of relapsed/refractory pediatric and adult acute lymphoblastic leukemia and refractory adult non-Hodgkin lymphoma, resulting in the expanded use of CAR T cells in multicenter trials and as US FDA-approved products. Cytokine release syndrome (CRS) and CAR-associated neurotoxicity, which can occur independently or concurrently with CRS, are two potentially life-threatening toxicities of CAR T-cell therapy. In this review, we will focus on describing the pathophysiology behind CRS, the proposed definitions of and grading systems for CRS, and innovative options for treating this potentially lethal systemic inflammatory condition.

Keywords: adoptive cellular immunotherapy, CD19 CAR T cells, tocilizumab, CAR-associated neurotoxicity, Immune Effector Cell-Associated Neurotoxicity Syndrome, leukemia

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