CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial
CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial
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BCMA靶向CAR-T治疗中CRS相关凝血病：I/II期临床试验的回顾性分析
DOI：
10.1038/s41409-021-01226-9
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发表时间：
2021-02-19
影响因子：
4.8
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Shao, Mi;Yu, Qin;Huang, He
靶向B细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T细胞疗法在治疗难治性/复发性多发性骨髓瘤（R/R MM）患者中显示出有希望的效果。在这项I/II期临床试验（ChiCTR 1800017404）的回顾性分析中，37例R/R MM患者在淋巴细胞清除化疗后接受了首次BCMA靶向CAR T细胞。有效率高（97%），同时伴随着凝血功能障碍等不良事件的发生率高。37例患者中，所有（100%）有细胞因子释放综合征（CRS），34例（91%）至少有一项凝血参数异常。血浆组织因子（TF）、因子X（FX）、因子XII（FXII）和P-选择素（P-selectin）水平与CRS严重程度及某些特异性细胞因子水平呈正相关，提示这些因素可能在CRS相关凝血功能障碍中起重要作用。本研究提示，CRS与凝血功能紊乱有一定的关系。此外，尽管凝血功能障碍的发生率很高，但可以通过日常监测和早期干预进行管理。
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.