Characteristics and Risk Factors of Cytokine Release Syndrome in Chimeric Antigen Receptor T Cell Treatment.

Abstract

Clinical trials have confirmed that chimeric antigen receptor (CAR) T cell therapies are revolutionizing approaches for treating several relapsed or refractory hematological tumors. Cytokine release syndrome (CRS) is an adverse event with high incidence during CAR-T treatment. A further understanding of the characteristics and related risk factors of CRS is important for effective management. A total of 142 patients with relapsed or refractory acute lymphocyte leukemia (ALL), lymphoma, or multiple myeloma (MM) received lymphodepletion chemotherapy followed by infusion of CAR-T cells. The characteristics of CRS at different time points after treatment were monitored and risk factors were analyzed. The incidence of CRS for ALL, lymphoma, and multiple myeloma were 82%, 90%, and 90% respectively. Fever was observed on a median of day 3 for ALL, day 1 for lymphoma, and day 8.5 for MM after CAR-T cell infusion, and the duration was different between grade 1-2 CRS and grade 3-5 CRS. Disease types, peak concentration of IL-6, and CRP were associated with CRS. For patients with ALL, numbers of lymphoblast in bone marrow before lymphodepletion, peak concentration of IL-6, and CRP were independent risk factors of CRS. Clinical stage of lymphoma patients and high tumor burden in marrow of MM patients were independent risk factors of CRS. In conclusion, the characteristics and risk factors of CRS in different B-cell hematological tumors are different and should be managed individually during CAR-T cell therapy.

• Authors: Zhiling Yan, Huanxin Zhang, Jiang Cao, Cheng Zhang, Hui Liu, Hongming Huang, Hai Cheng, Jianlin Qiao, Ying Wang, Yan Wang, Lei Gao, Ming Shi, Wei Sang, Feng Zhu, Depeng Li, Haiying Sun, Qingyun Wu, Yuekun Qi, Hujun Li, Xiangmin Wang, Zhenyu Li, Hong Liu, Junnian Zheng, Wenbin Qian, Xi Zhang, Kailin Xu
• Journal: Frontiers in immunology (Front Immunol) Vol. 12 Pg. 611366 ( 2021) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33708205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Yan, Zhang, Cao, Zhang, Liu, Huang, Cheng, Qiao, Wang, Wang, Gao, Shi, Sang, Zhu, Li, Sun, Wu, Qi, Li, Wang, Li, Liu, Zheng, Qian, Zhang and Xu.

Chemical References

• Biomarkers
• Receptors, Antigen, T-Cell
• Receptors, Chimeric Antigen

Topics

• Adolescent
• Adult
• Aged
• Biomarkers
• Cytokine Release Syndrome (diagnosis, etiology, metabolism)
• Disease Susceptibility
• Female
• Hematologic Neoplasms (complications, therapy)
• Humans
• Immunotherapy, Adoptive (adverse effects, methods)
• Male
• Middle Aged
• Neoplasm Staging
• Receptors, Antigen, T-Cell (immunology, metabolism)
• Receptors, Chimeric Antigen (immunology, metabolism)
• Risk Factors
• T-Lymphocytes (immunology, metabolism)
• Young Adult