What are the typical neurotoxicities associated with Chimeric Antigen Receptor T-cell (CAR-T) therapy?

From the Guidelines

Typical CAR-T neurotoxicities include immune effector cell-associated neurotoxicity syndrome (ICANS), which can manifest as encephalopathy with confusion and behavioral changes, expressive aphasia or other language disturbance, dysgraphia, dysarthria, fine motor impairment and other weakness, tremor, myoclonus, and headache, as reported in the 2021 ASCO guideline 1. The most common symptoms of ICANS are:

• Encephalopathy with confusion and behavioral changes
• Expressive aphasia or other language disturbance
• Dysgraphia
• Dysarthria
• Fine motor impairment and other weakness
• Tremor
• Myoclonus
• Headache These symptoms typically occur within the first 1-2 weeks after CAR-T cell infusion, often peaking around day 5-17, and can range from mild cognitive impairment to life-threatening cerebral edema 1. Management of ICANS includes:
• Close neurological monitoring using the 10-point Immune Effector Cell–Associated Encephalopathy (ICE) score 1
• Supportive care
• Corticosteroids for moderate to severe cases, as they are the mainstay of treatment for ICANS 1
• Evaluation of other neurologic domains including level of consciousness, severe motor weakness, seizures, and signs of elevated intracranial pressure or cerebral edema 1 It is essential to note that tocilizumab does not resolve ICANS and may worsen it, and therefore, its use should be avoided in the management of ICANS 1. Early recognition and prompt intervention are crucial for managing these potentially serious side effects of CAR-T therapy.

From the Research

Typical Neurotoxicities Associated with CAR-T Therapy

The typical neurotoxicities associated with Chimeric Antigen Receptor T-cell (CAR-T) therapy include:

• Cytokine release syndrome (CRS) 2, 3, 4, 5, 6
• Immune effector cell-associated neurotoxicity syndrome (ICANS) 2, 3, 4, 5, 6

Characteristics of ICANS

ICANS is characterized by:

• Delirium and language dysfunction 5
• Seizures 5
• Coma 5
• Fatal cerebral edema 5

Pathophysiology of Neurotoxicity

The pathophysiology of neurotoxicity associated with CAR-T therapy is not well understood, but it is thought to involve:

• Monocytes 4
• Endothelial dysfunction 4
• The blood-brain barrier 4
• Systemic and local cytokine release 5

Treatment and Prevention Strategies

Treatment and prevention strategies for neurotoxicity associated with CAR-T therapy include:

• Close monitoring 2, 3
• Measures of support 2, 3
• Anticonvulsivants 2, 3
• Corticosteroids 2, 3, 5, 6
• Early admission to intensive care 2, 3
• Blockade of IL-1 and IL-6 signaling 5