Predictors of low- and high-grade ICANS after CAR-T: A nationwide analysis.

Abstract

7036 Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a leading cause of morbidity following chimeric antigen receptor T-cell (CAR-T) therapy. However, the real-world predictors of severity remain incompletely defined. We evaluated whether ICANS risk differs between multiple myeloma (MM) and other CAR-T indications. Methods: CAR-T hospitalizations were identified using ICD-10-PCS procedure codes. ICANS was identified using ICD-10-CM grade-specific codes (G92.00–G92.05) and severity was graded as none, low-grade (1–2), or high-grade (3–5). The 2022–2023 Healthcare Cost and Utilization Project National Inpatient Sample (HCUP NIS) with discharge weights was used for this analysis. Multivariable multinomial (nominal) regression (reference outcome: no ICANS) estimated adjusted odds ratios (aORs) for low- and high-grade ICANS. Cancer type was modeled with MM as a reference and compared with lymphomas, leukemias, solid/metastatic malignancies, and unspecified/other malignancies, adjusting for prespecified comorbidities including dementia, diabetes, and substance use diagnoses. Results: Among 10,105 weighted CAR-T hospitalizations, the risk of high-grade ICANS varied significantly by cancer type. Relative to MM, high-grade ICANS was significantly higher in leukemia (aOR 5.23 (95% CI 3.81–7.16), p < 0.001); lymphoma (aOR 3.91 (95% CI 3.07–5.00), p < 0.001); solid/metastatic malignancy (aOR 1.92 (95% CI 1.30–2.83), p = 0.001); and unspecified/other malignancy (aOR 6.34, 95% CI 4.98–8.07, p < 0.001). For low-grade ICANS, lymphoma was associated with increased odds compared with MM (aOR 1.53, 95% CI 1.31–1.78; p<0.001). Comorbidity signals were dominated by baseline neurologic vulnerability and metabolic disease. Dementia was the strongest predictor of high-grade ICANS (aOR 7.54, 95% CI 4.13–13.78; p<0.001). Drug abuse was associated with increased odds of low-grade ICANS (aOR 2.68, 95% CI 1.45–4.97; p=0.002). Diabetes with complications was associated with both low-grade (aOR 1.49, 95% CI 1.24–1.79; p<0.001) and high-grade ICANS (aOR 1.63, 95% CI 1.33–1.99; p<0.001). Conclusions: In a nationally representative inpatient cohort, multiple myeloma (MM) was associated with significantly lower odds of high-grade ICANS compared with other CAR-T indications, especially leukemia and lymphoma. Dementia and complicated diabetes were highly predictive of high-grade ICANS across all cancer types. These findings identify a clinically actionable risk profile that may inform future risk-stratified monitoring and early intervention strategies as CAR-T use expands. Limitations include reliance on administrative ICD-10 coding, which may misclassify ICANS severity, the possibility of clinical confounding, and a lack of product-specific and other clinical granularity.