Brain Microstructural Damage as Potential Biomarker of Immune Cell-Associated Neurotoxicity Syndrome

Area of Science:

• Neuroscience
• Oncology
• Radiology

Background:

• Chimeric antigen receptor-engineered T-cell (CAR-T) therapy is a promising treatment for hematological malignancies.
• CAR-T therapy can lead to severe complications like Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS).
• Identifying patients at higher risk for ICANS is crucial for improving treatment safety.

Purpose of the Study:

• To investigate if pre-treatment MRI-derived macrostructural and microstructural features can predict ICANS risk in patients receiving CAR-T therapy.
• To assess the association between baseline MRI findings and the development of ICANS and CRS.

Main Methods:

• Brain MRIs, including diffusion-weighted imaging, were performed on 42 patients before CAR-T administration.
• General linear models compared baseline MRI features (macrostructural and microstructural) between patients who developed ICANS, CRS, or neither.
• Binary logistic regression analyzed the predictive role of microstructural features for ICANS risk.

Main Results:

• Fifty percent of patients developed ICANS (14/42), and 73.8% developed CRS (31/42).
• No significant differences in white matter hyperintensities or total brain volume were found between groups at baseline.
• Fractional anisotropy in white matter, both within and outside hyperintensities, predicted ICANS risk (p=0.03 and p=0.02, respectively).

Conclusions:

• Pre-treatment brain volume and white matter hyperintensities on MRI are not reliable predictors of ICANS.
• The severity of white matter microstructural (axonal) damage prior to CAR-T therapy is a significant predictor of ICANS risk.
• Greater axonal damage is associated with an increased likelihood of developing ICANS after CAR-T therapy.