Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome

噬血细胞性淋巴组织细胞增多症 免疫学 嵌合抗原受体 细胞因子释放综合征 血液学 免疫系统 医学 免疫失调 T细胞 痹症科 细胞激素风暴 细胞疗法 疾病 细胞 内科学 生物 传染病(医学专业) 遗传学 2019年冠状病毒病(COVID-19)
作者
Melissa Hines,Tristan Knight,Kevin O. McNerney,Mark B. Leick,Tania Jain,Sairah Ahmed,Matthew J. Frigault,Joshua A. Hill,Michael D. Jain,William T. Johnson,Yi Lin,Kris M. Mahadeo,Gabriela Marón,Rebecca Marsh,Sattva S. Neelapu,Sarah Nikiforow,Amanda K. Ombrello,Nirav N. Shah,Aimee C. Talleur,David P. Turicek,Anant Vatsayan,Sandy W. Wong,Marcela V. Maus,Krishna V. Komanduri,Nancy Berliner,Jan‐Inge Henter,Miguel‐Angel Perales,Noelle V. Frey,David T. Teachey,Matthew J. Frank,Nirali N. Shah
标识
DOI:10.1016/j.jtct.2023.03.006
摘要

T cell-mediated hyperinflammatory responses, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are now well-established toxicities of chimeric antigen receptor (CAR) T cell therapy. As the field of CAR T cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like toxicities following CAR T cell infusion are occurring broadly across patient populations and CAR T cell constructs. Importantly, these HLH-like toxicities are often not as directly associated with CRS and/or its severity as initially described. This emergent toxicity, however ill-defined, is associated with life-threatening complications, creating an urgent need for improved identification and optimal management. With the goal of improving patient outcomes and formulating a framework to characterize and study this HLH-like syndrome, we established an American Society for Transplantation and Cellular Therapy panel composed of experts in primary and secondary HLH, pediatric and adult HLH, infectious disease, rheumatology and hematology, oncology, and cellular therapy. Through this effort, we provide an overview of the underlying biology of classical primary and secondary HLH, explore its relationship with similar manifestations following CAR T cell infusions, and propose the term “immune effector cell-associated HLH-like syndrome (IEC-HS)” to describe this emergent toxicity. We also delineate a framework for identifying IEC-HS and put forward a grading schema that can be used to assess severity and facilitate cross-trial comparisons. Additionally, given the critical need to optimize outcomes for patients experiencing IEC-HS, we provide insight into potential treatment approaches and strategies to optimize supportive care and delineate alternate etiologies that should be considered in a patient presenting with IEC-HS. By collectively defining IEC-HS as a hyperinflammatory toxicity, we can now embark on further study of the pathophysiology underlying this toxicity profile and make strides toward a more comprehensive assessment and treatment approach.
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