Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy

AbstractThe CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has been widely proved effective on relapsed and refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL). Meanwhile, CAR-T therapy-related toxicities, including cytokine release syndrome (CRS) and neurological toxicities, are drawing researchers ’ attention. In addition, our research team notices that coagulopathy and even disseminated intravascular coagulation (DIC) are common problems during CAR-T therapy. In our phase 1/2 clinical trial (NCT02965092), 53 r/r B-ALL patients underwent leukapheresis on day − 11 and received lymphodepl eting chemotherapy on day − 7 to day − 5. Finally, they received split infusions of anti-CD19 CAR-T cells on day 0 to day 2. Plasma concentrations of tissue factor (TF) and platelet endothelial cell adhesion molecular-1 (PECAM-1) were also measured to identify the mechanism of coagulation di sorders. The overall 1-month remission rate of the 53 patients was 88.7%. During the treatment course, 19 patients experienced grade 3–4 CRS, 8 patients developed grade 2–3 neurological toxicities. Beyond that, 30 patients (30/53, 56.6%) suffered from coagulation disorders, and half of them shou ld be diagnosed as DIC. Benefiting from replacement and anticoagulant therapy, 14 patients successfully got out of the conditions of DIC. Remarkably, the severity of coagulopathy was positively correlated with CRS grade. What is more, plasma TF and PECAM-1 levels indicat...
Source: Annals of Hematology - Category: Hematology Source Type: research