Elrexfio

Dose reductions of Elrexfio are not recommended. Dose delays may be needed to manage toxicities.

Management of Cytokine Release Syndrome (CRS)

Identify CRS based on clinical presentation; evaluate and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold Elrexfio until CRS resolves. Give supportive therapy for CRS (eg, intensive care for severe or life-threatening CRS). Consider monitoring laboratory testing for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.  

CRS Grade 1 presenting with temperature ≥100.4°F (38°C)

• Withhold Elrexfio until CRS resolves.

• Give pretreatment medications prior to the next dose of Elrexfio.

CRS Grade 2 presenting with temperature ≥100.4°F (38°C) with either: Hypotension responsive to fluid and not requiring vasopressors, and/or oxygen requirement of low-flow nasal cannula or blow-by

• Withhold Elrexfio until CRS resolves.

• Monitor daily for 48 hours after the next dose of Elrexfio. Instruct patients to remain within proximity of a healthcare facility, and consider hospitalization.

• Give pretreatment medications prior to next dose of Elrexfio.

CRS Grade 3 (first occurrence) presenting with temperature ≥100.4°F (38°C) with either: Hypotension requiring 1 vasopressor with or without vasopressin, and/or oxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask

• Withhold Elrexfio until CRS resolves.

• Provide supportive therapy, which may include intensive care.

• Patients should be hospitalized for 48 hours after the next dose of Elrexfio.

• Give pretreatment medications prior to next dose of Elrexfio.

CRS Grade 3 (recurrent) presenting with temperature ≥100.4°F (38°C) with either: Hypotension requiring 1 vasopressor with or without vasopressin, and/or oxygen requirement of high-flow nasal cannula, facemask, non-rebreather mask, or Venturi mask

• Permanently discontinue treatment.

• Provide supportive therapy, which may include supportive care.

CRS Grade 4 presenting with temperature ≥100.4°F (38°C) with either: Hypotension requiring  multiple vasopressors (excluding vasopressin), and/or oxygen requirement of positive pressure (eg, CPAP, bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation)

• Permanently discontinue treatment.

• Provide supportive therapy, which may include supportive care.

Neurologic Toxicity Including ICANS

At first sign of neurologic toxicity, including ICANS, withhold Elrexfio and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS. 

ICANS Grade 1 presenting with: ICE score 7–9; or depressed level of consciousness: awakens spontaneously

• Withhold Elrexfio until ICANS resolves.

• Monitor neurologic symptoms and consider consulting with a neurologist and other specialists for further evaluation and management.

• Consider non-sedating, anti-seizure medications (eg, levetiracetam) for seizure prophylaxis.

ICANS Grade 2 presenting with: ICE score 3–6; or depressed level of consciousness: awakens to voice

• Withhold Elrexfio until ICANS resolves.

• Give dexamethasone 10mg IV every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.

• Monitor neurologic symptoms and consider consulting with a neurologist and other specialists for further evaluation and management.

• Consider non-sedating, anti-seizure medications (eg, levetiracetam) for seizure prophylaxis.

• Monitor daily for 48 hours after the next dose of Elrexfio. Instruct patients to remain with proximity of a healthcare facility, and consider hospitalization.

ICANS Grade 3 (first occurrence) presenting with: ICE score 0–2; or depressed level of consciousness: awakens only to tactile stimulus; or seizures, either: any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures or EEG that resolve with intervention

• Withhold Elrexfio until ICANS resolves.

• Give dexamethasone 10mg IV every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.

• Monitor neurologic symptoms and consider consulting with a neurologist and other specialists for further evaluation and management.

• Consider non-sedating, anti-seizure medications (eg, levetiracetam) for seizure prophylaxis.

• Give supportive therapy, which may include intensive care. 

• Monitor daily for 48 hours after the next dose of Elrexfio. 

ICANS Grade 3 (recurrent) presenting with: ICE score 0–2; or depressed level of consciousness: awakens only to tactile stimulus; or seizures, either: any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures or EEG that resolve with intervention; or raised intracranial pressure: focal/local edema on neuroimaging

• Permanently discontinue.

• Give dexamethasone 10mg IV every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper.

• Monitor neurologic symptoms and consider consulting with a neurologist and other specialists for further evaluation and management.

• Consider non-sedating, anti-seizure medications (eg, levetiracetam) for seizure prophylaxis.

• Give supportive therapy, which may include intensive care. 

ICANS Grade 4 (recurrent) presenting with: ICE score 0–2; or depressed level of consciousness either: patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma; or seizures, either: life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between; or motor findings: deep focal motor weakness such as hemiparesis or paraparesis; or raised intracranial pressure/cerebral edema, with signs/symptoms such as: diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing’s triad

• Permanently discontinue.

• Give dexamethasone 10mg IV every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Alternatively, consider methylprednisolone 1000mg per day IV for 3 days.

• Monitor neurologic symptoms and consider consulting with a neurologist and other specialists for further evaluation and management.

• Consider non-sedating, anti-seizure medications (eg, levetiracetam) for seizure prophylaxis.

• Give supportive therapy, which may include intensive care. 

Hematologic Adverse Reactions

Absolute neutrophil count (ANC) less than 0.5 x 10⁹/L: Withhold until ANC is ≥0.5 x 10⁹/L.

Febrile neutropenia: Withhold until ANC is ≥1 x 10⁹/L and fever resolves.

Hemoglobin less than 8 g/dL: Withhold until hemoglobin is ≥8 g/dL.

Platelet count less than 25,000/mcL, or Platelet count between 25,000/mcL and 50,000/mcL with bleeding: Withhold until platelet count is ≥25,000 and no evidence of bleeding.

Infections and Other Non-Hematologic Adverse Reactions

Grade 3: Withhold Elrexfio until adverse reaction improves to ≤Grade 1 or baseline.

Grade 4: Consider permanent discontinuation. If Elrexfio is not permanently discontinued, withhold subsequent treatment doses until adverse reaction improved to Grade 1 or less.