How I treat refractory CRS and ICANS after CAR T-cell therapy

Author(s): Michael D. Jain1;Melody Smith2;Nirali N. Shah3
Source: Blood (2023) 141 (20): 2430–2442
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Review(s) of the month. The May 18 issue of Blood has several well-done reviews on CAR-T toxicity management. As these treatments become more available, we will all need to be prepared to manage these unique adverse effects.


The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly because of the expanding indications for standard-of-care treatment and the development of new investigational products. The establishment of consensus diagnostic criteria for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), alongside the steady use of both tocilizumab and corticosteroids for treatment, have been essential in facilitating the widespread use. Preemptive interventions to prevent more severe toxicities have improved safety, facilitating CAR T-cell therapy in medically frail populations and in those at high risk of severe CRS/ICANS. Nonetheless, the development of persistent or progressive CRS and ICANS remains problematic because it impairs patient outcomes and is challenging to treat. In this case-based discussion, we highlight a series of cases of CRS and/or ICANS refractory to front-line interventions. We discuss our approach to managing refractory toxicities that persist or progress beyond initial tocilizumab or corticosteroid administration, delineate risk factors for severe toxicities, highlight the emerging use of anakinra, and review mitigation strategies and supportive care measures to improve outcomes in patients who develop these refractory toxicities.

Author Affiliations

1Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL;2Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA;3Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD

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