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Chapter 14 - Headache and Fever

Published online by Cambridge University Press:  24 April 2026

By
Brian Cameron and
Monica K. Wattana
Edited by
Angela Bray Lindsay and
Monica Kathleen Wattana
Angela Bray Lindsay
Affiliation:
Virginia Commonwealth University
Monica Kathleen Wattana
Affiliation:
University of Texas, MD Anderson Cancer Center
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Summary

1. Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) represent a spectrum of inflammatory side effects associated with T-cell targeted therapies, such as CAR-T.

2. Patients with CAR-T related CRS and/or ICANS toxicities have favorable prognosis and are expected to recover without persistent side-effects if symptoms are recognized early and managed rapidly. These toxicities are relatively reversible and require prompt collaboration between the ED provider, oncologist, and other specialists.

3. The American Society for Blood and Marrow Transplantation (ASTCT) grading scale is commonly utilized to characterize the severity of CRS and ICANS with management recommendations based on severity grade.

4. IL-6 inhibitors such as tocilizumab do not cross the blood-brain barrier and should not be used for ICANS treatment unless there is concomitant CRS.

5. Consider early transfer for higher level of care, even if patient has a low CRS grade, if IL-6 inhibitors are not available for administration at your hospital.

Keywords

Chimeric Antigen Receptor TherapyCytokine Release SyndromeNeurotoxicityImmune Effector Cell-Associated NeurotoxicityImmunotherapyaxicabtogene ciloleuceltisagenlecleucelbrexucabtagene autoleucellisocabtagene maraleucelidecabtagene vicleucelciltacabtagene autoleucelKymriahYescartaTecartusBreyanziCarvykti

Information

Type
Chapter
Information
Oncologic Emergency Medicine
Clinical Cases Illustrating Key Concepts
 , pp. 65 - 71
Publisher: Cambridge University Press
Print publication year: 2026

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References

Further Reading

Bellal, M, Malherbe, J, Damaj, G, Du Cheyron, D. Toxicities, intensive care management, and outcome of chimeric antigen receptor T cells in adults: an update. Crit Care. 2024;28:69. doi:10.1186/s13054-024-04851-0CrossRefGoogle ScholarPubMed
Garcia, Borrega, J, Godel, P, Ruger, MA, Onur, OA, Shimabukuro-Vornhagen, A, Kochanek, M, et al. In the eye of the storm: immune-mediated toxicities associated with CAR-T cell therapy. HemaSphere. 2019;3(2):e191. https://doi.org/10.1097/HS9.0000000000000191.CrossRefGoogle Scholar
Lipe, DN, Qdaisat, A, Chaftari, P, Wattana, MK, Krishnamani, PP, Reyes-Gibby, C, Yeung, SJ. Emergency department use by patients who received chimeric antigen receptor T cell infusion therapy. Front Oncol. 2023;13:1122329. https://doi.org/10.3389/fonc.2023.1122329. PMID: 37007139; PMCID: PMC10064130.CrossRefGoogle ScholarPubMed
Neelapu, SS. Managing the toxicities of CAR T-cell therapy. Hematol Oncol. 2019; 37(S1): 48–52. https://doi.org/10.1002/hon.2595.CrossRefGoogle ScholarPubMed
Rees, JH. Management of immune effector cell-associated neurotoxicity syndrome (ICANS). In Kröger, N, Gribben, J, Chabannon, C, Yakoub-Agha, I, Einsele, H (eds.), The EBMT/EHA CAR-T Cell Handbook. Springer 2022. https://doi.org/10.1007/978-3-030-94353-0_27.Google Scholar
Riegler, LL, Jones, GP, Lee, DW. Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy. Ther Clin Risk Manag. 2019;15:323–335. https://doi.org/10.2147/TCRM.S150524.CrossRefGoogle ScholarPubMed
Sheth, VS, Gauthier, J. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant. 2021;56:552–566. https://doi.org/10.1038/s41409-020-01134-4.CrossRefGoogle ScholarPubMed

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