Table 3.

Pharmacologic management of CRS and neurologic toxicities

Drug	Indication	Dose
Tocilizumab	Left ventricular ejection fraction <40% by echocardiogram;	4 to 8 mg/kg infused over 1 h, dose not to exceed 800 mg
	Creatinine >2.5-fold higher than the most recent level prior to CAR T-cell infusion;
	Norepinephrine requirement at a dose >2 μg/min for 48 h since the first administration of norepinephrine, even if administration is not continuous;
	SBP of 90 mm Hg that cannot be maintained with norepinephrine;
	Oxygen requirement of FiO2 >50% or more for more than 2 h continuously;
	Dyspnea that is severe enough to potentially require mechanical ventilation;
	Activated PTT >2× the upper limit of normal;
	Clinically-significant bleeding; and
	Creatine kinase >5× the upper limit of normal for longer than 2 d
Methylprednisolone	CRS toxicity refractory to tocilizumab	1-2 mg/kg IV every 12 h
Dexamethasone	Grade 3 neurologic toxicities, with the exception of headaches, that last continuously for 24 h or longer; Grade 4 neurologic toxicity of any duration; and	10 mg IV q 6 h until either:  Toxicities improved to grade 1 or  less, or  At least 8 doses have been given
	Any generalized seizure

These are the current treatment guidelines used for adult patients at the NCI Experimental Transplantation and Immunology Branch.

FiO2, fraction of inspired oxygen.