Table 1.

The management of CRS and ICANS with different grades.

Side Effects		Grade 1	Grade 2	Grade 3	Grade 4
CRS [84,85]	Fever or organ toxicity	Acetaminophen or Ibuprofen can be used as a treatment option for fever Assess for infection using blood and urine cultures, and chest radiography Empiric broad-spectrum antibiotics and filgrastim if neutropenic Maintenance of intravenous (i.v.) fluids for hydration Symptomatic management of constitutional symptoms and organ toxicities Tocilizumab or siltuximab ± corticosteroids
	Hypotension	Grading and supportive care	Echocardiogram; initiate other methods of hemodynamic monitoring i.v. fluid bolus of 500–1000 mL of normal saline Tocilizumab or siltuximab; tocilizumab can be repeated after 6 h if needed
			If hypotension persists after two fluid boluses and anti-IL-6 therapy, start vasopressors, and consider transfer to an intensive care unit	Monitoring in the intensive care unit
			In patients at high risk or hypotension persists after 1–2 doses of anti-IL-6 therapy, dexamethasone can be used at 10 mg i.v. every 6 h for 1–3 days	Dexamethasone at 10 mg i.v. every 6 h for 1–3 days If refractory, increase to 20 mg i.v. every 6 h	Methylprednisolone i.v. 1000 mg/day for 3 days 250 mg × 2/day for 2 days 125 mg × 2/day for 2 days 60 mg × 2/day for 2 days
	Hypoxia	Grading and supportive care	Tocilizumab or siltuximab ± corticosteroids and supportive care
			Supplemental oxygen	Supplemental oxygen, including high-flow oxygen delivery and non-invasive positive-pressure ventilation	Mechanical ventilation
ICANS [45,85]		Supportive care and neurological work-up: Aspiration precautions and i.v. hydration Seizure prophylaxis with levetiracetam EEG Brain imaging (MRI and CT) Spinal imaging for focal motor weakness Consider tocilizumab if there is concurrent CRS
			Transferring the patient to an intensive care unit if grade ≥ 2 CRS	Intensive care unit transfer	Intensive care unit monitoring; mechanical ventilation
			Dexamethasone at 10–20 mg i.v. every 6 h or its equivalent of methylprednisolone for 1–3 days.		Lower ICP with hyperventilation, hyperosmolar therapy with mannitol/hypertonic saline, and/or neurosurgery consultation for a ventriculoperitoneal shunt in patients with cerebral edema
				Control seizures with benzodiazepines (for short-term control) and levetiracetam +/− phenobarbital and/or lacosamide For focal/local edema, methylprednisolone i.v. 1000 mg/day for 3 days 250 mg × 2/day for 2 days 125 mg × 2/day for 2 days 60 mg × 2/day for 2 days

CRS: cytokine release syndrome; EEG: electroencephalogram; ICANs: immune-effector-cell-associated neurotoxicity syndrome; ICP: intracranial pressure; i.v.: intravenous injection.