TableÂ 4. Neurotoxicity grading and... | American Society of Hematology

TableÂ 4.

Neurotoxicity grading and proposed management for CD3×CD20 BsAbs

Definition: neurological AEs after BsAb therapy most frequently consist of headache and dizziness; occasionally, ICANS-like symptoms occur; these may or may not accompany CRS
Symptoms: delirium, dysgraphia, tremor, lethargy, difficulty concentrating, agitation, confusion, expressive aphasia, apraxia, depressed level of consciousness, encephalopathy, and seizures
Recommendations: patients and caregivers need to be educated on symptoms and patients cannot drive or operate heavy machinery if symptomatic
Workup and evaluation:

Pertinent history and PE
Review medications including last dose of antipyretic therapy, steroids, or anticytokine therapy
Perform ICE score on all patients with neurologic symptoms
Assess for alternate cause of symptoms; consider performing CT head, EEG, MRI, or LP, as appropriate
Assess for concurrent symptoms of CRS (fever, hypoxia, and hypotension); treatment of CRS can occur concurrently if appropriate
If any concern for neurological AEs exists, patient should be evaluated in outpatient center or ED. If any worsening symptoms (eg, somnolence, worsening confusion, weakness, etc), patients should be promptly referred to the ED

ICE scoring system

Orientation to year, month, city, hospital

4 points

Naming 3 objects

3 points

Following simple commands

1 point

Writing standard sentence

1 point

Attention to count backward from 100 by 10

1 point

ICANS grading

Management

Grade 1: ICE 7-9 or depressed level of consciousness but awakens spontaneously

Pending clinical scenario and social situation, can consider observation or close monitoring in outpatient setting. Can consider dexamethasone 10 mgÂ × 1

Grade 2: ICE 3-6 or depressed level of consciousness but awakens to voice

Admit patient to hospital for monitoring
Dexamethasone 10 mg IV every 12 h, followed by taper once grade ≥1

Grade 3: ICE 0-2 or depressed level of consciousness but awakens to tactile stimulus or any clinical seizure that resolves rapidly or focal/local edema on neuroimaging

Monitor in ICU setting
Neurology consult
Dexamethasone 10 mg IV every 6 h, followed by taper once gradeÂ ≥1
Use antiepileptics for seizure management as needed
Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue until resolution

Grade 4: ICE is 0 or patient is unarousable or requires vigorous or repetitive tactile stimuli, or life-threatening prolonged seizure (>5 min) or repetitive seizures without return to baseline or deep focal motor weakness or diffuse cerebral edema on neuroimaging

Monitor in ICU setting
Neurology consult
Dexamethasone 10 mg IV every 6 h, followed by taper once gradeÂ ≥1
Use antiepileptics for seizure management as needed
Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue until resolution

Definition: neurological AEs after BsAb therapy most frequently consist of headache and dizziness; occasionally, ICANS-like symptoms occur; these may or may not accompany CRS Symptoms: delirium, dysgraphia, tremor, lethargy, difficulty concentrating, agitation, confusion, expressive aphasia, apraxia, depressed level of consciousness, encephalopathy, and seizures Recommendations: patients and caregivers need to be educated on symptoms and patients cannot drive or operate heavy machinery if symptomatic Workup and evaluation: Pertinent history and PE Review medications including last dose of antipyretic therapy, steroids, or anticytokine therapy Perform ICE score on all patients with neurologic symptoms Assess for alternate cause of symptoms; consider performing CT head, EEG, MRI, or LP, as appropriate Assess for concurrent symptoms of CRS (fever, hypoxia, and hypotension); treatment of CRS can occur concurrently if appropriate If any concern for neurological AEs exists, patient should be evaluated in outpatient center or ED. If any worsening symptoms (eg, somnolence, worsening confusion, weakness, etc), patients should be promptly referred to the ED
ICE scoring system
Orientation to year, month, city, hospital	4 points
Naming 3 objects	3 points
Following simple commands	1 point
Writing standard sentence	1 point
Attention to count backward from 100 by 10	1 point
ICANS grading	Management
Grade 1: ICE 7-9 or depressed level of consciousness but awakens spontaneously	Pending clinical scenario and social situation, can consider observation or close monitoring in outpatient setting. Can consider dexamethasone 10 mgÂ × 1
Grade 2: ICE 3-6 or depressed level of consciousness but awakens to voice	Admit patient to hospital for monitoring Dexamethasone 10 mg IV every 12 h, followed by taper once grade ≥1
Grade 3: ICE 0-2 or depressed level of consciousness but awakens to tactile stimulus or any clinical seizure that resolves rapidly or focal/local edema on neuroimaging	Monitor in ICU setting Neurology consult Dexamethasone 10 mg IV every 6 h, followed by taper once gradeÂ ≥1 Use antiepileptics for seizure management as needed Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue until resolution
Grade 4: ICE is 0 or patient is unarousable or requires vigorous or repetitive tactile stimuli, or life-threatening prolonged seizure (>5 min) or repetitive seizures without return to baseline or deep focal motor weakness or diffuse cerebral edema on neuroimaging	Monitor in ICU setting Neurology consult Dexamethasone 10 mg IV every 6 h, followed by taper once gradeÂ ≥1 Use antiepileptics for seizure management as needed Consider adding anakinra 100 mg every 12 h if symptoms persist beyond 24 h, continue until resolution

CT, computed tomography; EEG, electroencephalogram; ICE, immune effector cell encephalopathy; ICU, intensive care unit; LP, lumbar puncture; MRI, magnetic resonance imaging; PE, physical examination.

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