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 |
| 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.