Coagulation Disorders after CAR T Cell Therapy: Analysis of 100 Patients with R/R Hematologic Malignancies

Abstract Chimeric antigen receptor (CAR)-T cell therapy, a new immunotherapy for relapsed and refractory (R/R) hematologic malignancies, can be accompanied by adverse events including coagulation disorders. Here, we performed a comprehensive analysis of coagulation parameters in 100 patients with R/R hematologic malignancies after receiving CAR-T cell therapy to illuminate the profiles of coagulation disorders, and to facilitate the management of coagulation disorders. A high incidence of coagulation disorders was observed, including elevated D-dimer (50/100, 50%), increased FDP (45/100, 45%), decreased fibrinogen (23/100, 23%), prolonged APTT (17/100, 17%), and prolonged PT (10/100, 10%). Coagulation disorders occurred mainly during day 6 and day 20 after CAR-T cell infusion. The changes of coagulation parameters were associated with high tumor burden in acute lymphoblastic leukemia (ALL), more lines of prior therapies, lower baseline platelet count, and especially cytokines released syndrome (CRS). Disseminated intravascular coagulation (DIC) was found in 7 patients with grade ≥3 CRS, and indicated a poor prognosis. Our study suggests that coagulation disorders are manageable in most patients after CAR-T cell therapy. Coexistence of DIC and severe CRS is closely related to non-relapsed deaths during the acute toxicity phase, and effective and timely treatment is the key to reduce non-relapse mortality for patients with DIC and severe CRS.