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

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, leukemi