CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 7; pp. 1642 - 1650
• Main Authors: Shao, Mi, Yu, Qin, Teng, Xinyi, Guo, Xin, Wei, Guoqing, Xu, Huijun, Cui, Jiazhen, Chang, A. H., Hu, Yongxian, Huang, He
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2021; Nature Publishing Group
• Subjects: 13/21; 13/31; 13/44; 631/250/251; 692/308/2779/109/1941; 82/1; Adverse events; Antigen receptors, T cell; Antigens; B-Cell Maturation Antigen; Blood clotting disorders; Blood Coagulation Disorders - etiology; Care and treatment; Cell Biology; Cell therapy; Cellular therapy; Chemotherapy; Chimeric antigen receptors; Clinical trials; Coagulation; Coagulation factors; Complications and side effects; Cytokine Release Syndrome; Cytokines; Health aspects; Hematology; Humans; Immunologic diseases; Immunotherapy, Adoptive; Inflammation; Interferon; Interleukin 10; Interleukins; Internal Medicine; Lymphocytes B; Lymphocytes T; Medicine; Medicine & Public Health; Multiple myeloma; Multiple Myeloma - therapy; P-selectin; Parameters; Patients; Public Health; Receptors; Receptors, Chimeric Antigen; Retrospective Studies; Risk factors; Stem cell transplantation; Stem Cells; T cells; Testing; Tissue factor; China
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-021-01226-9

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) has shown promising effects in the treatment of patients with refractory/relapsed multiple myeloma (R/R MM) patients. In this retrospective analysis of phase I/II clinical trial (ChiCTR1800017404), 37 patients with R/R MM received their first BCMA-targeted CAR T-cells following lymphodepletion chemotherapy. The response rate was high (97%), while accompanied by a high incidence of adverse events including coagulation dysfunction. Of 37 patients, all (100%) had cytokine release syndrome (CRS) and 34 (91%) developed at least one abnormal coagulation parameter. The values of coagulation parameters were positively correlated with the severity of CRS as well as with the levels of some cytokines, such as interleukin (IL)-6, IL-10, and interferon (IFN)-γ, etc. Furthermore, levels of the plasma tissue factor (TF), Factor X (FX), Factor XII (FXII), and P-selectin also showed a positive correlation with severity of CRS as well as some specific cytokines, which indicates that these factors are likely to play important roles in CRS-related coagulopathy. Our study suggests that there exists relationship in some extent between coagulation disorder and CRS. Moreover, coagulation dysfunction can be managed with daily monitoring and early intervention despite high incidence.