Comprehensive Neuroimaging and Molecular Biomarkers of Neurotoxicity Following CAR T-Cell Therapy

This is a prospective, open-label, single-arm study that aims to develop a novel tool for early identification of immune effector cell-associated neurotoxicity syndrome (ICANS) in patients undergoing chimeric antigen receptor (CAR) T-cell therapy for cancer.

ICANS, which is often referred to as neurotoxicity, is a syndrome affecting the brain and the nervous system. It can give headache, confusion, difficulty concentrating, lack of energy, agitation, tremors, difficulty with language, and seizures. Up to 70% of patients undergoing chimeric antigen receptor T-cell therapy experience this neurotoxicity syndrome. Although it typically resolves within the first month after chimeric antigen receptor T-cell therapy, some patients may develop delayed or long-lasting neurological problems.

In this study, the investigators will perform a comprehensive evaluation of participants undergoing chimeric antigen receptor T-cell therapy to study neurotoxicity. The study will use advanced neuroimaging techniques of brain magnetic resonance imaging; neurocognitive assessments; evaluation of quality of life; and blood collection to measure blood-based biomarkers. Biomarkers may be measured also in cerebrospinal fluid, if collected.

To obtain a comprehensive evaluation of brain activity, 3 different brain magnetic resonance imaging modalities will be employed: T1-post-contrast, T2/FLAIR, and diffusion-weighted sequences. In addition, resting state functional magnetic resonance imaging will be performed at the baseline visit and 3 months after chimeric antigen receptor T-cell therapy.

The magnetic resonance imaging data will be applied to 3D, U-Net-based convolutional neural network that is well-validated for the detection and segmentation of brain white matter hyperintensities. The convolutional neural network magnetic resonance imaging segmentation will be integrated with neurocognition and biomarkers data to develop a model for the diagnosis of ICANS that is more quantitative and standardized compared to the current qualitative standard.