- Instruct patients to remain within proximity of the certified healthcare facility for at least 4 weeks following infusion.

2.4     Management of Severe Adverse Reactions

Cytokine Release Syndrome  

Identify cytokine release syndrome (CRS) based on clinical presentation [see Warnings and Precautions (5.1)]. eva luate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 1.

Table 1. Treatment of CRS 

CRS Severity Management 

Prodromal Syndrome: 

Low-grade fever, fatigue, anorexia Observe in person; exclude infection; administer antibiotics per local guidelines if neutropenic; provide symptomatic support. 

CRS requiring mild intervention (one or more of the following): 

- High fever

- Hypoxia 

- Mild hypotension Administer antipyretics, oxygen, intravenous fluids and/or low-dose vasopressors as needed. 

CRS requiring moderate to aggressive intervention (one or more of the following): 

- Hemodynamic instability despite intravenous fluids and vasopressor support 

- Worsening respiratory distress, including pulmonary infiltrates increasing oxygen requirement including high-flow oxygen and/or need for mechanical ventilation 

- Rapid clinical deterioration • Administer high dose or multiple vasopressors, oxygen, mechanical ventilation and/or other supportive care as needed.

• Administer tocilizumab

- Patient weight less than 30 kg: 12 mg/kg intravenously over 1 hour

- Patient weight greater than or equal to 30 kg: 8 mg/kg intravenously over 1 hour (maximum dose 800 mg) 

Repeat tocilizumab as needed at a minimum interval of 8 hours if there is no clinical improvement.

If no response to second dose of tocilizumab, consider a third dose of tocilizumab or pursue alternative measures for treatment of CRS.

Limit to a maximum total of 4 tocilizumab doses.

• If no clinical improvement within 12 to 18 hours of the first tocilizumab dose, or worsening at any time, administer methylprednisolone 2mg/kg as an initial dose, then 2 mg/kg per day until vasopressors and high flow oxygen are no longer needed, then taper. 

3     DOSAGE FORMS AND STRENGTHS 

Pediatric and Young Adult r/r B-cell ALL (up to 25 years of age): A single dose of KYMRIAH contains 0.2 to 5.0 x 106 CAR-positive viable T cells per kg of body weight for patients 50 kg and below or 0.1 to 2.5 x 108 CAR-positive viable T cells for patients above 50 kg, suspended in a single patient-specific infusion bag [see How Supplied/Storage and Handling (16)].

Adult r/r DLBCL: A single dose of KYMRIAH contains 0.6 to 6.0 x 108 CAR-positive viable T cells, which may be suspended in one or more patient-specific infusion bag(s) [see How Supplied/Storage and Handling (16)].

See the CoA for actual cell count. The volume in the infusion bag ranges from 10 mL to 50 mL.

4     CONTRAINDICATIONS 

None.

5     WARNINGS AND PRECAUTIONS 

5.1     Cytokine Release Syndrome (CRS)