A comprehensive analysis of coagulopathy during anti-B cell maturation antigen chimeric antigen receptor-T therapy in multiple myeloma, a retrospective study based on LEGEND-2

Hematol Oncol. 2023 Oct;41(4):704-717. doi: 10.1002/hon.3155. Epub 2023 Apr 25.

Abstract

Chimeric antigen receptor (CAR)-reprogrammed T cell therapy is a novel and powerful treatment against hematological malignancies. Cytokine release syndrome (CRS) and other potentially life-threatening toxicities are known side effects which need appropriate management and supportive care. Coagulopathy is a common and severe CAR-T-related adverse event, while a comprehensive profile of coagulopathy in patients with multiple myeloma (MM) undergoing CAR-T cell therapy has not been reported. Therefore, we performed a comprehensive analysis of coagulopathy in 51 patients with r/r MM given anti-B cell maturation antigen CAR-T cell therapy. We found that 49% of patients had coagulation disorders, and 29% of patients experienced disseminated intravascular coagulation (DIC). Severe CRS, abnormal liver function and higher tumor burden were risk factors for the CAR-T-related coagulopathy. We found that the serum IL-6 level and alanine aminotransferase level were potential indicators for CAR-T-related DIC. Furthermore, we found that coagulation disorders occurred within 1 month after CAR-T cell infusion, mainly between days 10 and 13, which was 2-5 days later than the beginning of CRS and simultaneous with the beginning of abnormal liver function and the peak of CRS. In addition, although patients with coagulation dysfunction had a trend for better outcomes and prognosis, no statistical significance was found. In conclusion, our research provided a comprehensive understanding of CAR-T-related coagulopathy in MM. Upon timely and standardized treatment, coagulopathy was manageable in most cases.

Keywords: chimeric antigen receptor T cell; coagulopathy; cytokine release syndrome; disseminated intravascular coagulation; liver function; multiple myeloma.

MeSH terms

  • B-Cell Maturation Antigen / therapeutic use
  • Blood Coagulation Disorders* / complications
  • Blood Coagulation Disorders* / therapy
  • Cytokine Release Syndrome / etiology
  • Humans
  • Multiple Myeloma* / complications
  • Multiple Myeloma* / therapy
  • Receptors, Chimeric Antigen* / therapeutic use
  • Retrospective Studies

Substances

  • Receptors, Chimeric Antigen
  • B-Cell Maturation Antigen