Prolonged duration of lymphocyte deficiency, high-grade CRS, and ventilation are linked to fungal breakthrough in patients with hematologic malignancies 60 days after CAR-T infusion: A single center case-control study

Abstract

Background: Risk factors for invasive fungal infections (IFIs) after chimeric antigen receptor-modified T cells (CAR-T) treatment have been poorly studied. Here we are investigating the risk factors and prognosis of IFIs following CAR-T therapy.

Material and methods: A case-control study was conducted on the medical records of CAR-T patients admitted to our center between June 2018 and December 2020. The case group (32) consisted of patients who developed IFIs within 60 days after CAR-T infusion, while the control group (298) consisted of patients who did not develop IFIs. The Cox Proportional Hazard Regression model was utilized to analyze the risk factors for the occurrence of IFIs, as well as the factors affecting the 1-year survival rate of patients.

Result: Cumulatively, 364 patients were included. Inflammatory cytokine release syndrome (CRS) grade (hazard ratio (HR) 2.34 confidential interval (CI)（1.03-5.30) P = 0.042), ventilation (HR 3.23 CI (1.20-8.71) P = 0.020) and lymphocyte deficiency duration (HR 1.06 CI (1.01-1.10) P = 0.015) were associated with IFIs. IFIs (HR 1.12 CI (0.52-2.41) P = 0.767) did not affect a patient's one-year survival, which was associated with lymphocyte deficiency (HR 1.04 CI (1.01-1.07) P = 0.004) and treatment with broad-spectrum antibacterial (HR 1.80 CI (1.03-3.11) P = 0.038) within 30 days prior to CAR-T infusion.

Conclusion: There is an increased risk of IFIs in patients with hematologic malignancies due to ventilation, high-grade CRS, and prolonged lymphocyte deficiency within 60 days after CAR-T infusion. Invasive fungal infection was not a risk factor for death within 1 year of CAR-T therapy, while broad-spectrum antibacterial therapy prior to infusion and prolonged lymphocyte deficiency were risk factors.

Keywords: Case-control study; Chimeric antigen receptor-modified T cells; Cytokine release syndrome; Invasive fungal infections; Lymphocyte deficiency; Ventilation.