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

Bone Marrow Transplantation volume 56, pages 1642–1650 (2021)Cite this article

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Abstract

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.

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Fig. 1: The values of coagulation parameters at different time points.
Fig. 2: The changed values of coagulation parameters in patients with mild or severe CRS.
Fig. 3: The correlation between plasma coagulation factors, P-selectin and CRS.
Fig. 4: Schematic diagram of the relationship between CRS and coagulopathy.

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Acknowledgements

We thank all the study participants, especially the patients and their families. This work is supported by National Natural Science Foundation of China (81730008, 81770201, 81870153), the Key Project of Science and Technology Department of Zhejiang Province (2019C03016, 2018C03016-2).

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  1. These authors contributed equally: Mi Shao, Qin Yu, Xinyi Teng

Authors and Affiliations

  1. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Mi Shao, Xinyi Teng, Xin Guo, Guoqing Wei, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  2. Institute of Hematology, Zhejiang University, Hangzhou, China

    Mi Shao, Xinyi Teng, Xin Guo, Guoqing Wei, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  3. Zhejiang Province Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, China

    Mi Shao, Xinyi Teng, Xin Guo, Guoqing Wei, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  4. Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou, China

    Mi Shao, Xinyi Teng, Xin Guo, Guoqing Wei, Huijun Xu, Jiazhen Cui, Yongxian Hu & He Huang

  5. College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China

    Qin Yu

  6. Shanghai YaKe Biotechnology Ltd, Shanghai, China

    A. H. Chang

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Shao, M., Yu, Q., Teng, X. et al. CRS-related coagulopathy in BCMA targeted CAR-T therapy: a retrospective analysis in a phase I/II clinical trial. Bone Marrow Transplant 56, 1642–1650 (2021). https://doi.org/10.1038/s41409-021-01226-9

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