Early prediction of ICANS using CRS characteristics in B-cell lymphoma patients receiving CAR-T therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a serious early adverse event of chimeric antigen receptor T (CAR-T) cell therapy. ICANS typically occurs concurrently with or follows cytokine release syndrome (CRS), suggesting CRS can be considered the primary risk factor for ICANS onset. Therefore, CRS characteristics in an individual patient may predict their risk for subsequently developing ICANS. We analyzed 154 patients with B cell lymphoma treated with commercial CAR-T products between 2020 and 2024; 38 patients (24.7%) developed ICANS after CRS. The cohort was split into a derivation set and a validation set. In the derivation cohort, univariate analysis identified two CRS-related factors strongly associated with ICANS: CRS onset within 24h and grade 2-4 CRS by day 3. Using these two variables, we created a simple predictive model that stratified patients into high-, intermediate-, and low-risk groups, with ICANS incidences of 47.4%, 31.0%, and 8.2%, respectively. The validation cohort confirmed this trend. These findings suggest that early CRS characteristics provide a practical, clinically applicable method for estimating ICANS risk and may support timely management decisions in CAR-T therapy.