Table 1.
Comparison of criteria for NT grades between CTCAE, CARTOX-10 mCRES, and ASTCT scales
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | ||
|---|---|---|---|---|---|
| CTCAE | Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated | Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental ADL* | Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL† | Life-threatening consequences; urgent intervention indicated | |
| CARTOX CRES | Neurological score (by CARTOX-10) | 7-9 (mild impairment) | 3-6 (moderate impairment) | 0-2 (severe impairment) | Patient in critical condition, and/or obtunded and cannot perform assessment of tasks |
| Raised ICP | Not applicable | Not applicable | Stage 1-2 papilledema, or CSF opening pressure <20 mm Hg | Stage 3-5 papilledema, or CSF opening pressure ≥20 mm Hg, or cerebral edema | |
| Seizures or motor weakness | Not applicable | Not applicable | Partial seizure, or nonconvulsive seizures on EEG with response to benzodiazepine | Generalized seizures, or convulsive or nonconvulsive status epilepticus, or new motor weakness | |
| ASTCT ICANS‡ | ICE score¶ | 7-9 | 3-6 | 0-2 | 0: patient is unarousable and unable to perform ICE |
| Depressed and consciousness level§ | Awakens spontaneously | Awakens to voice | Awakens to tactile stimulation | Patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse. Stupor or coma | |
| Seizures and motor findings‖ | Not applicable | Not applicable | 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; deep focal motor weakness such as hemiparesis or paraparesis | |
| Elevated ICP/cerebral edema | Not applicable | Not applicable | Focal/local edema on neuroimaging** | Diffuse cerebral edema on neuroimaging; decerebrate or decorticate posturing; or cranial nerve VI palsy; or papilledema; or Cushing’s triad | |
ADL, activities of daily living; CSF, cerebrospinal fluid; EEG, electroencephalogram; ICP, intracranial pressure.
Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, and so on.
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not being bedridden.
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.
A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a patient with an ICE score of 0 may be classified grade 4 ICANS if unarousable.
Depressed level of consciousness should be attributable to no other cause (eD180X X gD181X X, no sedating medication).
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0, but they do not influence ICANS grading.
Intracranial hemorrhage with or without associated edema is not considered a NT feature and is excluded from ICANS grading. It may be graded according to CTCAE v5.0.