BACKGROUND: CD19-directed chimeric antigen receptor (CAR) T-cell therapy has markedly improved outcomes for patients with relapsed or refractory B-cell malignancies, although coagulopathy characterized by hypofibrinogenemia has increasingly been recognized as a complication after CAR T-cell therapy. Nevertheless, its contemporary real-world incidence, risk factors, and clinical impact remain incompletely defined. OBJECTIVE: This study aimed to determine the real-world incidence, risk factors, and clinical impact of hypofibrinogenemia following CD19-directed CAR T-cell therapy for relapsed or refractory B-cell lymphoma. STUDY DESIGN: This retrospective cohort study included all consecutive adult patients (≥16 years) with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL) who received tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), or axicabtagene ciloleucel (axi-cel) at Kyoto University Hospital between December 2019 and December 2024. We also evaluated detailed CRS severity according to modified CRS grading (m-CRS), in which grade 1 was subdivided into grade 1a (duration of CRS-related symptoms ≤5 days) and grade 1b (duration of CRS-related symptoms >5 days), as previously described; grade 1b CRS was defined as "prolonged CRS". RESULTS: A total of 111 patients (74 tisagenlecleucel tisa-cel 67%, 24 lisocabtagene maraleucel liso-cel 22%, and 13 axicabtagene ciloleucel axi-cel 12%) were included. Hypofibrinogenemia (fibrinogen ≤150 mg/dL) was observed in 28 patients (25%) within 30 days after infusion (median onset, 10.5 days). FFP was administered to 15 patients (14%). Multivariable analysis revealed that grade ≥1b CRS (adjusted hazard ratio aHR, 4.59; 95% confidence interval CI, 1.89-11.14; P < 0.01), lower baseline fibrinogen levels (aHR, 1.07 per 10 mg/dL decrease; 95% CI, 1.02-1.14; P = 0.01), and axi-cel use (vs. tisa-cel: aHR, 3.29; 95% CI, 1.38-7.83; P < 0.01) were independently associated with hypofibrinogenemia. In our cohort, no fatal bleeding events occurred. Hypofibrinogenemia was not associated with inferior overall survival or progression-free survival. CONCLUSION: Prolonged CRS (grade 1b) or grade ≥2 CRS, lower baseline fibrinogen, and use of axi-cel were independently associated with hypofibrinogenemia. Risk-adapted fibrinogen monitoring may help identify patients who could benefit from closer surveillance, and timely fibrinogen replacement may optimize supportive care. Further multicenter studies are warranted to validate these findings and clarify the clinical impact of hypofibrinogenemia, including hemorrhagic outcomes.
Bamba et al. (Fri,) studied this question.