Talvey

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 Talvey until CRS resolves or permanently discontinue based on severity, manage according to recommendations (see below). 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 Talvey until CRS resolves. Give pretreatment medications prior to the next dose of Talvey.

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

• Withhold Talvey until CRS resolves. Give pretreatment medications prior to next dose of Talvey. Patients should be hospitalized for 48 hours following the next dose of Talvey. 

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

• If duration is less than 48 hours: Withhold Talvey until CRS resolves. Provide supportive therapy, which may include intensive care. Give pretreatment medications prior to next dose of Talvey. Patients should be hospitalized for 48 hours after the next dose of Talvey. 

• Recurrent or duration greater than or equal to 48 hours: 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); 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 Talvey 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 Talvey 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 Talvey 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 Talvey. 

ICANS Grade 3 presenting with: ICE score 0–2 (If ICE score is 0, but the patient is arousable [eg, awake with global aphasia and able to perform assessment]); 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 on EEG that resolve with intervention; or raised intracranial pressure – focal/local edema on neuroimaging.

• First occurrence of Grade 3 ICANS: Withhold Talvey 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.  Patients should be hospitalized for 48 hours after the next dose of Talvey. 

• Recurrent Grade 3 ICANS: Permanently discontinue. Give dexamethasone 10mg IV every 6 hours and repeat dose 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 presenting with: ICE score 0 (Patient is arousable and unable to perform ICE assessment); or depressed level of consciousness – patient is unarousable to requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma; or seizures – life-threatening prolonged seizure (>5min), or repetitive clinical or electrical seizures without return to baseline in between; or motor findings – deep focal motor weakness (eg, 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 and repeat dose 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.

Oral Toxicity and Weight Loss

• Grade 1–2: Provide supportive care. Consider withholding Talvey if not responsive to supportive care.

• Grade 3: Withhold Talvey until resolution to Grade 1 or better and provide supportive care.

• Grade 4: Permanently discontinue Talvey.

Infections

• All Grades: Withhold Talvey in the step-up phase in patients until infection resolves.

• Grade 3: Withhold Talvey during the treatment phase until infection improves to Grade 1 or better within 28 days.

• Grade 4: Consider permanent discontinuation. If not discontinued, withhold subsequent doses until adverse reaction improves to Grade 1 or better.

Cytopenias

• ANC less than 0.5 x 10⁹/L: Withhold Talvey until ANC is 0.5 x 10⁹/L or higher.

• Febrile neutropenia: Withhold Talvey until ANC is 1.0 x 10⁹/L or higher and fever resolves.

• Hemoglobin less than 8 g/dL: Withhold Talvey until hemoglobin is 8 g/dL or higher.

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

Skin Reactions

• Grade 3 to 4: Withhold Talvey until reaction improves to Grade 1 or baseline.

Other Non-Hematologic Adverse Reactions

• Grade 3: Withhold Talvey until adverse reaction improves to Grade 1 or baseline.

• Grade 4: Consider permanent discontinuation. If not discontinued, withhold subsequent doses until adverse reaction improves to Grade 1 or better.