Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Epidemiology

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Etiology

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Physiology

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Diagnosis

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Clinical Manifestations

Neurologic Manifestations

Altered Mental Status

Epidemiology
- Association with Cytokine Release Syndrome (see Cytokine Release Syndrome)
  - Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Usually Occurs in the Context of Cytokine Release Syndrome, with Neurologic Symptoms Beginning within 2-4 Days of the Onset of Cytokine Release Syndrome
  - However, Cytokine Release Syndrome is Not Required for Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and the Syndromes Can Occur at Different Points in Time
Clinical
- General Comments
  - Degree and Type of Neurologic Involvement is Variable (Cancer Discov, 2017) [MEDLINE] (Cancer Discov, 2018)[MEDLINE] (J Neuropathol Exp Neurol, 2018) [MEDLINE] (Biol Blood Marrow Transplant, 2019) [MEDLINE] (Blood, 2019) [MEDLINE]
- Onset
  - Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Most Commonly Develops within 3-10 Days After Chimeric Antigen Receptor T (CAR-T) Cell Administration, But the Timing Can Vary Among CAR-T Cell Products and Disease Indications (Cancer Discov, 2017) [MEDLINE] (Cancer Discov, 2018) MEDLINE [MEDLINE] (Neuro Oncol, 2023) [MEDLINE]
  - Clinical Symptoms Can Be Rapidly Progressive within Hours-Few Days
- Auditory/Visual Hallucinations (see Hallucinations)
- Cerebral Edema/Malignant Cerebral Edema (see Increased Intracranial Pressure)
- Delirium/Confusion/Behavioral Changes (see Delirium)
- Dysgraphia/Fine Motor Impairment (see Dysgraphia)
- Encephalopathy (see Obtundation/Coma)
- Fatigue (see Fatigue)
- Headache (see Headache)
- Language Dysfunction/Speech Alterations/Apraxia (see Apraxia)
  - Inattention/Language Deficits Commonly Occur Early in the Course
- Seizures (see Seizures)
  - Seizures May Be Clinical/Subclinical (Including Status Epilepticus)
- Tremors (see Tremors)
Treatment
- Acute symptoms of ICANS are considered reversible and usually resolve within 7 to 10 days of onset with adequate management
  - Nevertheless, neurotoxicity can be life threatening and/or extended, with some patients requiring prolonged intensive care unit (ICU) monitoring and mechanical ventilation for airway protection and management of elevated intracranial pressure (ICP)
  - In fatal cases, the cause of death has primarily been attributed to malignant cerebral edema (J Neuropathol Exp Neurol, 2018) [MEDLINE] (Neurology, 2018) [MEDLINE]

Treatment

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References

General

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Clinical Manifestations

Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discov. 2017;7(12):1404 [MEDLINE]
Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia. Cancer Discov. 2018;8(8):958 [MEDLINE]
Neuropathology of a Case With Fatal CAR T-Cell-Associated Cerebral Edema. J Neuropathol Exp Neurol. 2018;77(10):877 [MEDLINE]
Cerebral edema secondary to chimeric antigen receptor T-cell immunotherapy. Neurology. 2018;91(18):843 [MEDLINE]
ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625 [MEDLINE]
Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells. Blood. 2019;133(20):2212 [MEDLINE]
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells. Neuro Oncol. 2023;25(12):2239 [MEDLINE]