Hypofibrinogenemia in Patients Receiving CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Large B Cell Lymphoma: A Single Institution Experience

Abstract

<h3>Background</h3> Hypofibrinogenemia can occur after Chimeric Antigen Receptor (CAR) T-cell therapy and is sometimes associated with cytokine release syndrome. Hypofibrinogenemia is associated with increased risk of bleeding as well as thrombosis. Limited literature exists on the incidence, complications and management of hypofibrinogenemia after CAR T-cell therapy. <h3>Methods</h3> We analyzed medical records on 148 patients who received CD19-directed CAR T-cell therapy for large B-cell lymphomas between 05/2015 and 09/2019. All patients who had at least one serum fibrinogen level measured in the first 30 days after CAR T-cell infusion were included in the analysis. All patients with serum fibrinogen < 200 mg/dL [lowest normal value] had data collected on abnormalities in other coagulation parameters including PTT, PT, INR at the time of nadir serum fibrinogen level. <h3>Results</h3> Out of 148 patients, 35 had at least one serum fibrinogen level measured in the first 30 days after CAR T-cell infusion. Nadir serum fibrinogen was < 200 mg/dl in 15/35 patients: 0-100 mg/dl in 9/15 and 100-200 mg/dl in 6/15. At the time of nadir fibrinogen level, 2/15 patients had abnormalities seen in the other 3 coagulation parameters. Of the 15 patients that had serum fibrinogen level < 200 mg/dl, four had a bleeding event and one had a thrombotic event within first 30 days after CAR T-cell infusion but none of these patients had a low fibrinogen level at the time of the bleed. Given concern for increased risk of bleeding, patients with serum fibrinogen level less than 100 mg/dl were given cryoprecipitate infusions. Details of the abnormalities in the coagulation parameters are highlighted in the table. <h3>Conclusions</h3> This study describes in detail, hypofibrinogenemia seen in patients treated with CD19-directed CAR T-cell therapy in lymphoma. None of the patients experienced a major bleeding or thrombotic event with low serum fibrinogen level. These descriptive data may be used by clinicians to inform their management of hypofibrinogenemia seen in CAR T-cell patients.