Current and emerging pharmacotherapies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis-like syndrome due to CAR T cell therapy.

Autor:	Walton ZE; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Division of Rheumatology, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Frigault MJ; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Maus MV; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	Expert opinion on pharmacotherapy [Expert Opin Pharmacother] 2024 Feb; Vol. 25 (3), pp. 263-279. Date of Electronic Publication: 2024 Apr 10.
DOI:	10.1080/14656566.2024.2340738
Abstrakt:	Introduction: Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of multiple hematologic malignancies. Engineered cellular therapies now offer similar hope to transform the management of solid tumors and autoimmune diseases. However, toxicities can be serious and often require hospitalization. Areas Covered: We review the two chief toxicities of CAR T therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the rarer immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. We discuss treatment paradigms and promising future pharmacologic strategies. Literature and therapies reviewed were identified by PubMed search, cited references therein, and review of registered trials. Expert Opinion: Management of CRS and ICANS has improved, aided by consensus definitions and guidelines that facilitate recognition and timely intervention. Further data will define optimal timing of tocilizumab and corticosteroids, current foundations of management. Pathophysiologic understanding has inspired off-label use of IL-1 receptor antagonism, IFNγ and IL-6 neutralizing antibodies, and janus kinase inhibitors, with data emerging from ongoing clinical trials. Further strategies to reduce toxicities include novel pharmacologic targets and safety features engineered into CAR T cells themselves. As these potentially curative therapies are used earlier in oncologic therapy and even in non-oncologic indications, effective accessible strategies to manage toxicities are critical.
Databáze:	MEDLINE
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