1. To evaluate ICANS characteristics, toxicity interventions, and clinical outcomes in MCL patients after CAR T-cell therapy 

2. To compare pre/post infusion Brain MRI, EEGs, and laboratory studies from MCL patients experiencing ICANS

CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, high rates of immune effector cell-associated neurotoxicity syndrome (ICANS) remain a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS following CD19 CAR T-cell therapy in MCL patients.

All patients (n=26) who received standard of care brexucabtagene autoleucel from October 2020 to July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. 

Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (≥ grade 3) ICANS. All ICANS patients had cytokine release syndrome (CRS), but there was no correlation between ICANS and CRS grades. 92% of EEGs revealed abnormal patterns including mild-severe slowing and other interictal changes, but without frank seizure. Seven (86%) of eight severe ICANS patients with pre and post-infusion scans demonstrated a range of acute DWI, T2 FLAIR, and ASL findings on brain MRI. These findings were often at the brain-cerebrospinal fluid (CSF) borders. Grade 3+ ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. Severe ICANS did not affect progression free survival (PFS) or overall survival (OS).

Grade 3+ ICANS occurred in 38% of MCL patients after CD19 CAR T-cell therapy. Severe ICANS is associated with acute post-infusion brain MRI findings near brain border tissues, and frequently abnormal EEG tracings. There was no discernible impact on treatment response and overall survival.