To characterize novel risk factors for the development of ICANS after treatment with chimeric antigen receptor (CAR)-T Cell therapy for management of cancer.

ICANS is a common immune-related neurological toxicity from CAR-T cell therapy, with up to a third of cases being considered severe, grade 3 or 4. High tumor burden and product dose are implicated in the development of ICANS, but there are still many unknowns. As such, precise models are lacking for identifying high-risk patients ahead of treatment.

We retrospectively reviewed all subjects who received FDA-approved CAR-T cells at a single institution from 2018 to 2023. We documented baseline inflammatory markers, autoimmune history, MRI brain findings, neurological exams, and Montreal Cognitive Assessment (MOCA) scores. We are using statistical analysis and modeling to predict relationships between baseline clinical, radiological, and serological findings and the development of ICANS. We are assessing the relationship between treatments of cytokine release syndrome (CRS) and development of ICANS.

We identified approximately 100 qualifying subjects, and to-date, analysis of 52 subjects showed 30% rate of ICANS, with 36% having had grade 3-5. There was a trend towards a higher risk of ICANS in those with lower KPS and higher baseline MOCA. Baseline elevated c-reactive protein (CRP) was associated with greater risk of ICANS (p = 0.02), but no relationship was found with baseline ferritin.  We will further report on the incidence of ICANS: 1) after CRS by grade, 2) after receiving tocilizumab for ICANS, 3) by nervous system involvement of cancer and location, 4) by presence of abnormal brain MRI, 5) by baseline neuro exam, and 6) by autoimmune history, personal and family. 

We will use the results to report novel risks and potentially protective factors for development of ICANS.