Keeping an eye on immune effector cell-associated neurotoxicity syndrome (ICANS): Outcomes and predictors of mortality.

Abstract

e23090 Background: CAR-T cell therapy has become a valuable tool in treatment of certain hematologic malignancies. Immune Effector Cell-Associated Neurotoxicity Syndrome(ICANS) is a potentially fatal neurotoxicity associated with CAR-T cell therapy. We sought to investigate the predictors, severity, and outcomes in different types of CAR-T causing ICANS. Methods: We analyzed data from the National Inpatient Sample-2022 and identified patients admitted to the hospital for CAR-T cell therapy using STATA BE 18.0 software. In this cohort, we isolated patients who developed ICANs using ICD-10 codes. We compared the baseline characteristics of patients who developed ICANS with those who did not after receiving CAR-T cell therapy. Subgroup analysis was performed based on type of CAR-T cell therapy and grades of ICANS. The primary endpoint was in-hospital mortality, stratified by the presence of ICANS. We also examined other outcomes such as length of stay (LOS) and total charge (TOTCH). Multivariate regression analysis was performed to identify independent risk factors of mortality. Results: Among 3,910 CAR-T cell therapy admissions in 2022, Axicabtagene Ciloleucel was the most frequently used (52%), followed by Idecabtagene Vicleucel (17%) and Brexucabtagene Autoleucel (14%). ICANS occurred in 20% (n = 780) of patients, with grade 3 being most common (38%). Demographically, ICANS patients were older (mean age 62 vs 59, p = 0.01), the cohort was predominantly white (73%), with 77% treated at large academic hospitals. Insurance coverage included 46% private insurance and 42% Medicare. Patients who received Axicabtagene Ciloleucel had higher prevalence of ICANS (58% vs 37%, p < 0.01). Pre-existing malnutrition (29% vs 16%, p < 0.01) and ischemic stroke (3% vs 1%, p = 0.02) were more prevalent in ICANS patients. ICANS patients had longer LOS (20 vs 14 days, p < 0.01) and higher TOTCH ($1,668,698 vs $1,400,089, p = 0.04). The in-hospital mortality for those with ICANS patients was 4% vs 2%(p = 0.06). Significant predictors of mortality in ICANS patients included pre-existing malnutrition (OR 8, 95% CI 3-21), pneumonia (OR 21, 95% CI 4-79), and seizures (OR 10, 95% CI 1.7-60). Conclusions: ICANS remains a significant complication of CAR-T cell therapy affecting 1 in 5 hospitalized patients. Identifying risk factors like nutritional status, history of stroke, and seizures is important in hospitalized patients. Management plan based on type of CAR-T cell therapy can improve overall outcomes. Proactive monitoring and early intervention in high-risk patients will help mitigate the risk and impact of ICANS.