Table 2.

Clinical management of CRS in CAR T-cell treatment of B-NHL^29,30

CRS grade	Patient monitoring	Supportive care	Cytokine antagonists	Corticosteroids	Plasmapheresis
Grade 1	Assess vital signs at least 3 times daily	Acetaminophen and a cooling blanket are the first choice for treatment of fever Ibuprofen can be a second choice for treatment of fever, if not contraindicated Blood cultures, urinalysis, urine cultures, and chest radiography should be ordered for assessment of infections Start empiric broad-spectrum antibiotics and G-CSF for patients with neutropenia Maintain IV fluids to keep patients well-hydrated Provide symptomatic management of organ toxicities	IL-6R antagonists can be considered prophylaxis (recommended)	Not recommended	Not recommended
Grade 2	Assess vital signs with continuous electrocardiogram monitoring	Provide IV fluid bolus as needed If hypotension persists after 2 fluid boluses and anti-IL-6 therapy, start vasopressors, consider ICU transfer, perform echocardiography, and initiate other methods of hemodynamic monitoring Manage fever and constitutional symptoms as in grade 1 Provide supplemental oxygen Perform symptomatic management of organ toxicities	Use one type of cytokine antagonist Recommended antibodies include: IL-6R antagonist (recommended) TNF-α antibody (exploratory recommendation) TNF-α receptor antibody (exploratory recommendation)	For persistent refractory symptoms after one type of cytokine antagonist therapy, consider: Dexamethasone 10 mg IV q6h (recommended)	Not recommended
Grade 3	Assess vital signs with continuous electrocardiogram monitoring Consider transferring the patient to the ICU for further monitoring and treatment	Provide IV fluid boluses and vasopressors as needed Transfer to the ICU, and perform echocardiography and hemodynamic monitoring Manage fever and constitutional symptoms as indicated for grade 1 CRS Provide supplemental oxygen, including high-flow oxygen delivery and noninvasive positive pressure ventilation Perform symptomatic management of organ toxicities	Use 2 or 3 types of cytokine antagonists together. Recommended antibodies include: IL-6R antagonist (recommended) TNF-α antibody (exploratory recommendation) TNF-α receptor antibody (exploratory recommendation)	For persistent refractory symptoms after 2 or 3 types of cytokine antagonist therapy, consider: Dexamethasone 10–20 mg IV q6h (recommended)	If cytokine therapy is ineffective or corticosteroid is contraindicated, order plasmapheresis evaluation of blood transfusion (exploratory recommendation)
Grade 4	Assess vital signs with continuous electrocardiogram monitoring ICU transfer for further monitoring and treatment is recommended	Provide IV fluids and vasopressors, and perform hemodynamic monitoring Manage fever and constitutional symptoms as in grade 1 CRS Provide mechanical ventilation Perform symptomatic management of organ toxicities	Use 3 types of cytokine antagonists together. Recommended antibodies include: IL-6R antagonist (recommended) TNF-α antibody (exploratory recommendation) TNF-α receptor antibody (exploratory recommendation)	Consider: Dexamethasone 20 mg IV q6h (recommended) Methylprednisolone IV 1 g/day (recommended)	Order plasmapheresis after evaluation of blood transfusion (recommended)

CRS, cytokine-release syndrome; CAR, chimeric antigen receptor; B-NHL, B-cell non-Hodgkin lymphoma; G-CSF, granulocyte colony-stimulating; IV, intravenous; IL-6R, interleukin 6 receptor; ICU, intensive care unit; TNF-α, tumor necrosis factor-α.