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Proposed grading for CAR-T cell-related immune effector cell-associated neurotoxicity syndrome (ICANS) from the ASTCT

Proposed grading for CAR-T cell-related immune effector cell-associated neurotoxicity syndrome (ICANS) from the ASTCT
Neurotoxicity domain Grade 1 Grade 2 Grade 3 Grade 4
ICE score* 7 to 9 3 to 6 0 to 2 0 (patient is unarousable and unable to perform ICE)
Depressed level of consciousness Awakens spontaneously Awakens to voice Awakens only to tactile stimulus Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse; stupor or coma
Seizure N/A N/A Any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on EEG that resolve with intervention Life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between
Motor findingsΔ N/A N/A N/A Deep focal motor weakness such as hemiparesis or paraparesis
Elevated ICP/cerebral edema N/A N/A Focal/local edema on neuroimaging Diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing triad
ICE score definitions
Orientation Orientation to year, month, city, hospital 4 points
Naming Ability to name 3 objects (eg, point to clock, pen, button) 3 points
Following commands Ability to follow simple commands (eg, "Show me 2 fingers" or "Close your eyes and stick out your tongue") 1 point
Writing Ability to write a standard sentence (eg, "Our national bird is the bald eagle") 1 point
Attention Ability to count backwards from 100 by 10 1 point
ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised ICP/cerebral edema) not attributable to any other cause; for example, a patient with an ICE score of 3 who has a generalized seizure is classified as grade 3 ICANS.
ASTCT: American Society for Transplantation and Cellular Therapy (formerly the American Society for Blood and Marrow Transplantation); ICE: immune effector cell-associated encephalopathy (based on orientation, naming, ability to follow commands, writing, and attention; refer to UpToDate text); N/A: not applicable; EEG: electroencephalogram; ICP: intracranial pressure; CTCAE: Common Terminology Criteria for Adverse Events.
* A patient with an ICE score of 0 (ie, not oriented, can't name 3 objects, can't follow simple commands, unable to write a sentence, and can't hold attention; refer to UpToDate text) may be classified as grade 3 ICANS if awake with global aphasia, but a patient with an ICE score of 0 may be classified as grade 4 ICANS if unarousable.
¶ Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication).
Δ Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE version 5.0, but they do not influence ICANS grading.
Intracranial hemorrhage, with or without associated edema, is not considered a neurotoxicity feature and is excluded from ICANS grading. It may be graded according to CTCAE version 5.0.
Original table modified for this publication. From: Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant 2019; 25:625. Table used with the permission of Elsevier Inc. All rights reserved.
Graphic 122197 Version 2.0

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