The risk factors for coagulation disorder of chimeric antigen receptor-T cell therapy in patients with hematological tumors: A systematic review and meta-analysis

Abstract

BACKGROUND: Currently, the frequency of coagulation dysfunction associated with chimeric antigen receptor-T cell (Car-T) therapy cannot yet be determined. OBJECTIVE: We performed a systematic review and meta-analysis to examine the prevalence of abnormal laboratory tests related to coagulation disorders in patients receiving Car-T therapy and provide a reference for future risk assessment mechanisms. METHODS: We searched PubMed, Embase, and Web of Science for relevant studies and evaluated their quality using the methodology index of non-random research (MINORS). 2672 quotations were retrieved via systematic searches. After screening of titles, abstracts and full-text, 45 trials involving 2541 patients were ultimately included. 41 studies reported the incidence of thrombocytopenia, 8 studies reported the rate of low fibrin, 4 trials reported the rate of APTT or PT abnormalities and only 3 trials reported the incidence of venous thromboembolism (VTE). We performed a quantitative meta-analysis to explore the incidence of thrombocytopenia following Car-T treatment. The incidence of hypofibrinogenemia, VTE, and abnormal APTT or PT was only qualitatively assessed, as fewer reports were included in this study. RESULTS: The overall incidence of thrombocytopenia associated with Car-T therapy was 45.8% (95%[CI], 0.384–0.533). The highest rates of thrombocytopenia occurred in patients with multiple myeloma (60.1%, 95%[CI], 0.507–0.688) and aged between 18 to 60 (50%, 95%[CI], 0.367–0.633). There was greater prevalence of thrombocytopenia in BCMA-Car-T therapy of 58.7% (95%[CI], 0.482–0.685). Thrombocytopenia occurred most frequently in Car-T patients treated with a dosage of 1 × 105–1 × 106 cell/kg, at a rate of 66.2% (95%[CI], 0.561–0.749). CONCLUSION: Overall, 45.8 percent of patients receiving Car-T treatment suffered from thrombocytopenia. Multiple myeloma patients, ages between 18–60, a dose of 1 × 105–1 × 106 cell/kg and BCMA-Car-T therapy are all considered high-risk factors.