Neurotoxicity Biology and Management

Area of Science:

• Immunology
• Oncology
• Neuroscience

Background:

• Chimeric antigen receptor (CAR) T-cell therapy is effective for hematological cancers.
• CAR T-cell therapy is linked to cytokine release syndrome and neurotoxicity.
• Immune effector cell-associated neurotoxicity syndrome (ICANS) is a significant toxicity of T-cell therapies.

Purpose of the Study:

• To review the incidence, clinical features, risk factors, biomarkers, pathophysiology, and management of ICANS.
• To highlight the poorly understood pathophysiology of ICANS.
• To discuss current understanding and future directions for ICANS.

Main Methods:

• Review of clinical trial experience.
• Analysis of animal models.
• Synthesis of existing literature on ICANS.

Main Results:

• ICANS is a clinical and neuropsychiatric syndrome occurring after T-cell therapies.
• Endothelial cell dysfunction, myeloid cells, blood-brain barrier disruption, and CNS cytokine elevation are implicated in ICANS.
• Clinical characteristics of ICANS are described, but pathophysiology and management strategies require further research.

Conclusions:

• ICANS is a critical challenge in CAR T-cell therapy.
• Further research into ICANS pathophysiology is essential for treatment and prevention.
• A comprehensive understanding of ICANS is needed to optimize patient outcomes.