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Axicabtagene Ciloleucel Dosage

Medically reviewed by Drugs.com. Last updated on Nov 19, 2020.

Usual Adult Dose for Lymphoma

2 x 10(6) chimeric antigen receptor (CAR)-positive viable T cells IV per kg body weight via IV infusion; infuse within 30 minutes

Maximum Dose: 2 x 10(8) CAR-positive viable T cells

Comments:
-Pretreatment: Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 IV and fludarabine 30 mg/m2 IV on the fifth, fourth, and third day before infusion of this drug.
-Premedication: Administer acetaminophen 650 mg orally and diphenhydramine 12.5 mg IV or orally approximately 1 hour before infusion of this drug.
-Avoid prophylactic use of systemic corticosteroids as it may interfere with the activity of this drug.

Use: Treatment of relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

CYTOKINE RELEASE SYNDROME (CRS):
-Identify CRS based on clinical presentation.
-Evaluate for and treat other causes of fever, hypoxia, and hypotension.
-If CRS is suspected, manage according to CRS grading.
-Patients who experience Grade 2 or higher CRS (e.g., hypotension, not responsive to fluids, or hypoxia requiring supplemental oxygenation) should be monitored with continuous cardiac telemetry and pulse oximetry.
-For patients experiencing severe CRS, consider performing an echocardiogram to assess cardiac function.
-For severe or life-threatening CRS, consider intensive care supportive therapy.

TABLE 1:
CRS GRADING:
GRADE 1 (symptoms require symptomatic treatment only [e.g., fever, nausea, fatigue, headache, myalgia, malaise]): No adjustment recommended.
GRADE 2 (symptoms require and respond to moderate intervention; oxygen requirement less than 40% FiO2 or hypotension responsive to fluids or low dose of one vasopressor or Grade 2 organ toxicity:
-Tocilizumab: Administer 8 mg/kg IV over 1 hour (not to exceed 800 mg) every 8 hours as needed if not responsive to IV fluids or increasing supplemental oxygen; limit to a maximum of 3 doses in 24 hours; maximum total of 4 doses.
-Corticosteroids: Manage per Grade 3 if no improvement within 24 hours after starting tocilizumab.
GRADE 3 (symptoms require and respond to aggressive intervention; oxygen requirement greater than or equal to 40% FiO2 or hypotension requiring high-dose or multiple vasopressors or Grade 3 organ toxicity or Grade 4 transaminitis:
-Tocilizumab: Administer 8 mg/kg IV over 1 hour (not to exceed 800 mg) every 8 hours as needed if not responsive to IV fluids or increasing supplemental oxygen; limit to a maximum of 3 doses in 24 hours; maximum total of 4 doses.
-Corticosteroids: Administer methylprednisolone 1 mg/kg IV 2 times a day or equivalent dexamethasone (e.g., 10 mg IV every 6 hours); continue corticosteroids use until the event is Grade 1 or less, then taper over 3 days.
GRADE 4 (life-threatening symptoms; requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD) or Grade 4 organ toxicity (excluding transaminitis):
-Tocilizumab: Administer 8 mg/kg IV over 1 hour (not to exceed 800 mg) every 8 hours as needed if not responsive to IV fluids or increasing supplemental oxygen; limit to a maximum of 3 doses in 24 hours; maximum total of 4 doses.
-Corticosteroids: Administer methylprednisolone 1000 mg IV daily for 3 days; if improves, then manage as detailed for Grade 3.

NEUROLOGIC TOXICITY:
Grade 2 or Higher:
-Monitor patients for neurologic toxicities (Table 2).
-Rule out other causes of neurologic symptoms.
-Patients who experience Grade 2 or higher neurologic toxicities should be monitored with continuous cardiac telemetry and pulse oximetry.
-Provide intensive care supportive therapy for severe or life-threatening neurologic toxicities. Consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis for any Grade 2 or higher neurologic toxicities.

TABLE 2:
NEUROLOGIC TOXICITY GRADING AND MANAGEMENT GUIDANCE:
GRADE 2:
-Concurrent CRS: Administer tocilizumab per Table 1 for management of Grade 2 CRS; if no improvement within 24 hours after starting tocilizumab, administer dexamethasone 10 mg IV every 6 hours if not already taking other corticosteroids; continue dexamethasone use until the event is Grade 1 or less, then taper over 3 days; consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
-No concurrent CRS: Administer dexamethasone 10 mg IV every 6 hours; continue dexamethasone use until the event is Grade 1 or less, then taper over 3 days; consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
GRADE 3:
-Concurrent CRS: Administer tocilizumab per Table 1 for management of Grade 2 CRS; in addition, administer dexamethasone 10 mg IV with the first dose of tocilizumab and repeat every 6 hours; continue dexamethasone use until the event is Grade 1 or less, then taper over 3 days; consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
-No concurrent CRS: Administer dexamethasone 10 mg IV every 6 hours; continue dexamethasone use until the event is Grade 1 or less, then taper over 3 days; consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
GRADE 4:
-Concurrent CRS: Administer tocilizumab per Table 1 for management of Grade 2 CRS; administer methylprednisolone 1000 mg IV per day with first dose of tocilizumab and continue methylprednisolone 1000 mg IV per day for 2 more days; if improves, then manage as above; consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.
-No concurrent CRS: Administer methylprednisolone 1000 mg IV per day for 3 days; if improves, then manage as above; consider non-sedating, anti-seizure medicines (e.g., levetiracetam) for seizure prophylaxis.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Yescarta. It includes elements to assure safe use and an implementation system. For additional information: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES:
Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, has been reported:
Recommendations:
-Do not administer this drug to patients with active infection or inflammatory disorders.
-Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, have been reported, including concurrently with CRS or after CRS resolution:
Recommendations:
-Monitor for neurologic toxicities during therapy.
-Provide supportive care and/or corticosteroids, as needed.
This drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the YESCARTA REMS.

CONTRAINDICATIONS:
-None

Safety and efficacy have not been established in patients younger than 18 years.
This drug is not recommended for use in children.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:
-This drug is for autologous and IV use only.
-Use central venous access for drug infusion.
-Infuse this drug by either gravity or a peristaltic pump; do not use a leukodepleting filter.
-Before infusing this drug, thaw it at approximately 37 degrees Celsius using either a water bath or dry thaw method until there is no visible ice in the infusion bag.
-Ensure tocilizumab and emergency equipment are available prior to drug infusion and during the recovery period.
-Administer this drug at a certified healthcare facility.
-Refer to the administration instructions in the manufacturer product information before infusing this drug.

Storage requirements:
-Store this drug frozen in the vapor phase of liquid nitrogen (minus 150 degrees Celsius or less); thaw before using.
-Once thawed, this drug may be stored at room temperature (20 to 25 degrees Celsius) for up to 3 hours.

Reconstitution/preparation techniques:
-Consult the manufacturer product information for instructions on preparing this drug for IV infusion.

General:
-This drug is for autologous use only. The patient's identity must match the patient identifiers on the cassette and infusion bag. Do not infuse this drug if the information on the patient-specific label does not match the intended patient.
-This drug is not indicated for the treatment of primary central nervous system lymphoma.
-Each single infusion bag of this drug contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL.
-In addition to T cells, this drug contains 5% dimethylsulfoxide (DMSO) and 2.5% albumin (human); it may contain NK and NK-T cells as well.
-Follow universal precautions and local biosafety guidelines for handling and disposal of this drug to avoid potential transmission of infectious diseases.

Monitoring:
-Hematologic: Blood counts (after drug infusion)
-Immunologic: Signs/symptoms of cytokine release syndrome (at least daily for 7 days following drug infusion, then for 4 weeks after infusion); immunoglobulin levels (after drug treatment)
-Infections/Infestations: Signs/symptoms of infection (before and after drug infusion); screening for HBV, HCV, and HIV (before collection of cells for manufacturing)
-Nervous System: Signs/symptoms of neurologic toxicities (at least daily for 7 days following drug infusion, then for 4 weeks after infusion)
-Oncologic: Secondary malignancies (life-long)

Patient advice:
-For at least 4 weeks after you receive an infusion of this drug, stay close to the certified healthcare facility where the drug was given to you.
-Avoid potentially dangerous activities such as driving and operating machinery for at least 8 weeks after receiving an infusion of this drug.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions