Table 5. Management of Immune Effector Cell–Associated Neurotoxicity Syndrome.

Grade	Presenting symptoms	Actions
Grade 1	ICE score 7–9, or depressed level of consciousness: awakens spontaneously	Withhold teclistamab-cqyv until ICANS resolves. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting nonsedating, antiseizure medicines for seizure prophylaxis.
Grade 2	ICE score 3–6, or depressed level of consciousness: awakens to voice	Withhold teclistamab-cqyv until ICANS resolves. Administer dexamethasone 10 mg intravenously every 6 hours; continue dexamethasone use until resolution to grade 1 or less then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting nonsedating, antiseizure medicines for seizure prophylaxis. Patients should be hospitalized for 48 hours following the next dose of teclistamab-cqyv.
Grade 3	ICE score 0–2, or depressed level of consciousness: awakens only to tactile stimulus, or seizures, either: Any clinical seizure, focal or generalized, that resolves rapidly Non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention or raised intracranial pressure: focal/local edema on neuroimaging	First occurrence of grade 3 ICANS: Withhold teclistamab-cqyv until ICANS resolves. Administer dexamethasone 10 mg intravenously every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting nonsedating, antiseizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Patients should be hospitalized for 48 hours following the next dose of teclistamab-cqyv. Recurrent grade 3 ICANS: Permanently discontinue teclistamab-cqyv. Administer dexamethasone 10 mg intravenously and repeat dose every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting nonsedating, antiseizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.
Grade 4	ICE score 0, or depressed level of consciousness: either: Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse Stupor or coma or seizures, either: Life-threatening prolonged seizure (> 5 minutes) Repetitive clinical or electrical seizures without return to baseline in between, or motor findings: Deep focal motor weakness such as hemiparesis or paraparesis or raised intracranial pressure/cerebral edema, with signs/ symptoms such as: Diffuse cerebral edema on neuroimaging Decerebrate or decorticate posturing Cranial nerve VI palsy Papilledema Cushing's triad	Permanently discontinue teclistamab-cqyv. Administer dexamethasone 10 mg intravenously and repeat dose every 6 hours; continue dexamethasone use until resolution to grade 1 or less, then taper. Alternatively, consider administration of methylprednisolone 1,000 mg per day intravenously and continue methylprednisolone 1,000 mg per day intravenously for 2 or more days. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting nonsedating, antiseizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care.

Note. ICANS = immune effector cell-associated neurotoxicity syndrome; ICE = immune effector cell-associated encephalopathy. If patient is arousable and able to perform ICE Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points. Grading based on the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS. Information from Janssen Biotech, Inc. (2022).