ICANS After CAR-T Therapy: Mechanisms and Management With a Focus on Corticosteroid-Refractory ICANS

Area of Science:

• Oncology
• Immunology
• Neurology

Background:

• Chimeric antigen receptor T (CAR-T) cell therapy offers a transformative approach for relapsed or refractory hematologic malignancies.
• Immune effector cell-associated neurotoxicity syndrome (ICANS) is a significant and potentially fatal complication of CAR-T cell therapy.
• A subset of patients experiences inadequate response or worsening of ICANS despite standard corticosteroid treatment, termed steroid-refractory ICANS.

Purpose of the Study:

• To summarize the cytokine-mediated mechanisms driving ICANS.
• To outline product-specific risk patterns and early recognition strategies for ICANS.
• To critically evaluate emerging investigational treatments for steroid-refractory ICANS.

Main Methods:

• Review of current literature on ICANS pathogenesis and management.
• Analysis of risk factors including CAR construct design, target antigen, and disease context.
• Appraisal of diagnostic tools for multimodal risk assessment (e.g., ICE score, EASIX, cytokine profiles).

Main Results:

• ICANS involves a cascade of cytokine release, endothelial activation, blood-brain barrier disruption, and neuroinflammation.
• Risk stratification tools require further validation for predictive accuracy.
• Emerging therapies target cytokine pathways, endothelial stabilization, and CAR-T cell activity.

Conclusions:

• Understanding ICANS mechanisms is crucial for managing CAR-T cell therapy complications.
• Early recognition and risk assessment are vital for timely intervention.
• Novel therapeutic strategies show promise for managing refractory ICANS, offering hope for improved patient outcomes.