Predictors and Outcomes of Immune Effector Cell Associated Neurotoxicity Syndrome in Patients Receiving Chimeric Antigen Receptor T Cell Therapy for Aggressive B-Cell Non-Hodgkin Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment for patients with aggressive relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). One notable complication is immune effector cell-associated neurotoxicity syndrome (ICANS) which can be life-threatening. Treatment includes supportive care along with corticosteroids, often for protracted time periods. While ICANS presentation can be variable, it was previously unknown whether patients experiencing ICANS and treated with steroids had reduced CAR-T cell activity and worse outcomes. In addition, the optimal predictors of severe ICANS prior to lymphodepletion remain incompletely understood with a few studies suggesting utility of the endothelial stress activation index (EASIX) score or the modified EASIX score (m-EASIX). We conducted a multicenter retrospective analysis of 352 patients who received axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for the treatment of B-NHL. In this cohort 125 patients developed ICANS (35.5%). Survival was not different among patients who did not develop ICANS, with median PFS of 4.1 months (vs 9.5 months in those who developed ICANS, P = 0.37) and median OS in patients who did not develop ICANS was 25.3 (vs 15.2 months in those who developed ICANS, P = 0.16). Evaluation of the EASIX and m-EASIX scores in our data set demonstrated limited discriminatory ability in predicting development of ICANS (AUC 0.64 and 0.66 respectively). Additionally, CRP alone performed similarly to these scores (AUC 0.64), highlighting the need for novel predictive models for severe ICANS which might aid in appropriate product selection and lead to strategies to prevent neurologic toxicity after CAR-T treatment.