Cytokine Release Syndrome in Patients Treated With Chimeric Antigen Receptor T-cell Therapy: A Retrospective Study Analyzing Risks, Outcomes, and Healthcare Burden.

ABSTRACT

Background Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapy for various malignancies. However, its use is associated with challenges, including cytokine release syndrome (CRS), a potentially severe complication. This retrospective study aims to analyze the risks, outcomes, and healthcare burden of CRS in patients undergoing CAR-T therapy. Method Data from the 2020 National Inpatient Sample (NIS) were utilized, comprising 415 CAR-T-related hospitalizations. They were categorized into those with CRS (n = 68) and those without CRS (n = 347). Baseline characteristics, including age, gender, race, income, insurance status, and comorbidities, were compared. Outcomes of interest included in-hospital mortality, length of stay (LOS), total hospital charges, and access to complications, associations, and interventions. Statistical analyses, including multivariable models, were employed to assess associations. Results Hospitalizations with CRS did not exhibit significant differences in age, gender, race, income, or insurance status compared to those without CRS. The multivariable analysis showed no statistically significant difference in mortality (adjusted odds ratio (aOR) = 2.48, 95% confidence interval (CI) 0.71 to 8.69, p = 0.151), LOS (coefficient = -2.1 days, 95% CI -5.43 to 1.21, p = 0.207), or total hospital charges (coefficient = $207,456, 95% CI $6119 to $421,031, p = 0.057) between the two groups. The CRS group had a higher incidence of fever (aOR = 1.91, 95% CI 1.15 to 3.17, p = 0.014), acute respiratory failure (aOR = 2.10, 95% CI 1.01 to 4.40, p= 0.049), and the need for intubation/mechanical ventilation (aOR = 2.59, 95% CI 1.14 to 5.88, p = 0.024). Hemophagocytic lymphohistiocytosis (HLH) was significantly associated with CRS (aOR = 6.72, 95% CI 2.03 to 22.18, p = 0.002). Conclusion While the development of CRS in CAR-T-treated patients did not significantly increase mortality, LOS, or total hospital charges, it was associated with specific risks and outcomes, including fever, respiratory failure, and HLH. This study emphasizes the importance of vigilance in recognizing and managing CRS in CAR-T therapy to optimize patient outcomes. The findings contribute valuable insights to guide clinical decision-making in the context of CAR-T therapy.