Posted: Friday, October 21, 2022
An article published in Blood Advances presented an analysis of coagulation and fibrinolysis parameters related to the infusion of the cellular immunotherapy tisagenlecleucel present in the peripheral blood of patients with refractory or relapsed diffuse large B-cell lymphoma (DLBCL). Souichi Adachi, MD, PhD, of Kyoto University, Japan, and colleagues reported a significant elevation in the plasma level of total plasminogen activator inhibitor, which seems to promote the initial step of coagulopathy.
“A well-known adverse event after CAR-T therapy is cytokine-release syndrome [CRS]…. However, CRS-related coagulopathy…has not yet been studied widely,” stated Dr. Adachi and colleagues.
A total of 25 patients who received tisagenlecleucel infusion were enrolled in this study. Blood samples were collected before lymphocyte-depletion chemotherapy and on days 3 and 13 after chimeric antigen receptor T-cell infusion. Comprehensive analyses were performed to assess coagulation and fibrinolysis. These parameters included but were not limited to complete blood cell counts, fibrinogen, elastase-derived crosslinked fibrin degradation products, antithrombin, thrombin-antithrombin complex, and soluble fibrin.
Overall findings revealed a significant elevation in total plasminogen activator inhibitor (P = .02) at the onset of CRS. Additional findings revealed that suppressed fibrinolysis induced a relative hypercoagulable state, which was gradually resolved after remission of CRS without any organ damage (P < .01).
Based on these findings, the study authors stated that subclinical coagulopathy required no further treatment maneuvers in their cohort and that this may explain why coagulopathy with tisagenlecleucel treatment in patients with mild CRS was sometimes overlooked. Overall, they concluded, their results would facilitate further understanding of CRS-related coagulopathy and emphasize the importance of continued monitoring of sequential coagulation and fibrinolysis parameters during CAR T-cell therapy.
Disclosure: For full disclosures of the study authors, visit bloodadvances.org.