CAR-T 细胞治疗所致细胞因子释放综合征、神经毒性与噬血细胞性淋巴组织细胞增生症样综合征的现有及新兴药物治疗

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, IFN 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.