Axicabtagene ciloleucel parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of axicabtagene ciloleucel.
Drugs List
Therapeutic Indications
Uses
Large B-cell lymphoma
Adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
Adults with primary mediastinal large B-cell lymphoma (PMBCL) after two or more lines of systemic therapy.
Dosage
Whilst the typical dose stated below is given as recommended by the manufacturer, local cancer network protocols and product literature should also be consulted.
Adults
Pre-treatment (lymphodepleting chemotherapy)
500mg cyclophosphamide per metre squared (intravenous), and 30mg fludarabine per metre squared (intravenous) should be administered on the 5th, 4th and 3rd days before axicabtagene ciloleucel infusion.
Pre-medication
500mg to 1g paracetamol (oral) and 12.5mg to 25mg diphenhydramine (intravenous or oral) should be administered approximately 1 hour before axicabtagene ciloleucel infusion.
Axicabtagene ciloleucel infusion
A dose of axicabtagene ciloleucel should typically contain 2 million CAR-positive viable T cells per kg of bodyweight, up to a maximum of 200 million cells.
Additional Dosage Information
Management of cytokine release syndrome (CRS)
Grade 1
Symptomatic treatment only.
Grade 2
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum 800mg intravenously over 1 hour. Repeat as necessary every 8 hours (if patient is unresponsive to intravenous fluids or increasing supplemental oxygen), up to a maximum of 3 doses in a 24 hour period, or a maximum of 4 doses total.
Steroids: No action needed for 24 hours after initiating tocilizumab. If symptoms persist beyond 24 hours, manage as per grade 3.
Grade 3
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum 800mg intravenously over 1 hour. Repeat as necessary every 8 hours (if patient is unresponsive to intravenous fluids or increasing supplemental oxygen), up to a maximum of 3 doses in a 24 hour period, or a maximum of 4 doses total.
Steroids: Administer 1mg/kg methylprednisolone intravenously twice a day. If CRS resolves to grade 1 or lower, taper corticosteroids over 3 days. If CRS does not resolve to grade 1 or lower, manage as per grade 4.
Grade 4
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum 800mg intravenously over 1 hour. Repeat as necessary every 8 hours (if patient is unresponsive to intravenous fluids or increasing supplemental oxygen), up to a maximum of 3 doses in a 24 hour period, or a maximum of 4 doses total.
Steroids: Administer 1000mg methylprednisolone intravenously daily for 3 days. If CRS improves, manage as per grade 3. If CRS does not improve, consider alternative immunosuppressants.
Management of neurologic adverse reactions
Without concurrent cytokine release syndrome (CRS)
Grade 1
No action needed.
Grade 2
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam). Administer 10mg dexamethasone intravenously every 6 hours. If neurologic reactions resolve to grade 1 or lower, taper dexamethasone over 3 days.
Grade 3
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam). Administer 10mg dexamethasone intravenously every 6 hours. If neurologic reactions resolve to grade 1 or lower, taper dexamethasone over 3 days.
Grade 4
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam). Administer 1000mg methylprednisolone intravenously per day for 3 days. If neurologic adverse reactions improve, manage as per grade 3.
With concurrent cytokine release syndrome (CRS)
Grade 1
Symptomatic treatment only.
Grade 2
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam).
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum 800mg intravenously over 1 hour. Repeat as necessary every 8 hours (if patient is unresponsive to intravenous fluids or increasing supplemental oxygen), up to a maximum of 3 doses in a 24 hour period, or a maximum of 4 doses total.
Dexamethasone: No action needed for 24 hours after initiating tocilizumab. If symptoms persist beyond 24 hours, administer 10mg dexamethasone intravenously and repeat every 6 hours (if not already taking other corticosteroids). Continue dexamethasone until adverse events resolve to grade 1 or less, then taper over 3 days.
Grade 3
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam).
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum 800mg intravenously over 1 hour. Repeat as necessary every 8 hours (if patient is unresponsive to intravenous fluids or increasing supplemental oxygen), up to a maximum of 3 doses in a 24 hour period, or a maximum of 4 doses total.
Dexamethasone: Administer 10mg dexamethasone intravenously alongside the first dose of tocilizumab and repeat every 6 hours. Continue dexamethasone until adverse events resolve to grade 1 or less, then taper over 3 days.
Grade 4
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam).
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum 800mg intravenously over 1 hour. Repeat as necessary every 8 hours (if patient is unresponsive to intravenous fluids or increasing supplemental oxygen), up to a maximum of 3 doses in a 24 hour period, or a maximum of 4 doses total.
Steroids: Administer 1000mg methylprednisolone intravenously alongside the first dose of tocilizumab. Continue 1000mg methylprednisolone per day for 2 more days. If symptoms improve, manage as per grade 3.
Administration
Axicabtagene ciloleucel should be prepared according to the manufacturer's instructions and using appropriate precautions. It should then be administered by intravenous infusion centrally.
Axicabtagene ciloleucel is strictly for autologous use only.
Contraindications
Children under 18 years
Graft-versus-host-disease
Inflammatory disorder
Uncontrolled systemic infection
Within 6 weeks of live vaccines
Hepatitis B
Hepatitis C
Positive HIV status
Pregnancy
Primary CNS lymphoma
Severe cardiac disorder
Severe hypotension
Severe pulmonary disease
Precautions and Warnings
Breastfeeding
Cardiac impairment
Dehydration
Hepatic impairment
History of central nervous system disorder
History of seizures
Pulmonary disease
Renal impairment
Avoid live vaccines during treatment and until immune recovery
Before initiating treatment screen all patients for HBV, HCV and HIV
Cytokine release syndrome may require immunosuppressive treatment
Neurological toxicity may require immunosuppressive treatment
Advise patient not to drive/operate machinery for 8 weeks after treatment
Consider pre-medication with antihistamines and/or antipyretics
Consider premedication with hypouricaemic agent
Maintain adequate hydration of patient prior / during treatment
Not suitable for CD19 -ve patients who relapsed on prior anti-CD19 therapy
Treatment to be initiated and supervised by a specialist
Contains dimethyl sulfoxide (DMSO)
May contain trace amounts of gentamicin
Consult local policy on the safe use of anti-cancer drugs
Emergency equipment must be available
Febrile neutropenia should be treated with broad spectrum IV antibiotics
For autologous use only
Record name and batch number of administered product
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor differential blood count
Monitor for and manage hepatitis reactivation during treatment
Monitor for hypersensitivity reactions - risk of severe reactions
Monitor for hypogammaglobulinaemia and manage accordingly
Monitor for signs of cytokine release syndrome daily, for at least 10 days
Monitor for signs of Macrophage Activation Syndrome (MAS)
Monitor for signs of neurological toxicity
Monitor patient constantly for signs of new infection
Monitor patients for signs of tumour lysis syndrome
Monitor patients life-long for secondary malignancies
Advise patient to report signs of haemophagocytic lymphohistiocytosis (HLH)
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Antimicrobial prophylaxis recommended if severe neutropenia occurs
Consider cardiac telemetry/pulse oximetry if CRS/neurologic reaction occurs
Female: Ensure adequate contraception during treatment
Advise patient to avoid donating blood, organs, tissues or cells
Advise patient to remain near a clinical facility for 4weeks after infusion
Prophylactic use of systemic steroids may interfere with axicabtagene ciloleucel activity, and as such is not recommended.
Gloves and glasses should be worn to avoid the transmission of infectious blood-borne diseases.
As axicabtagene ciloleucel is strictly for autologous use only, it must be verified before infusion that the patient's identity matches the identifiers on the cassette label and bag label.
Axicabtagene ciloleucel must not be irradiated.
Cytokine release syndrome (CRS) and neurologic adverse events are common observed reactions to axicabtagene ciloleucel treatment. In addition to normal management, patients experiencing grade 2 or higher reactions should be monitored with continuous cardiac telemetry and pulse oximetry. Intensive care supportive therapy and echocardiograms to assess cardiac function should be considered for patients experiencing severe or life-threatening reactions. Diagnosis of CRS requires elimination of other potential causes of systemic inflammatory response, including infection. Febrile neutropenia may be concurrent with CRS, and should be managed with broad spectrum antibiotics, fluids and other supportive care.
Ensure at least 1 dose of tocilizumab is available for each patient prior to infusing axicabtagene ciloleucel for use in the event of cytokine release syndrome. The treatment centre must have access to additional doses of tocilizumab within 8 hours of each previous dose. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the MHRA Central Alerting System, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
Pregnancy and Lactation
Pregnancy
Axicabtagene ciloleucel is contraindicated during pregnancy.
The manufacturer contraindicates the use of axicabtagene ciloleucel in pregnancy. At the time of writing there is limited published information regarding the use of axicabtagene ciloleucel during pregnancy. There is a theoretical risk that transduced cells from axicabtagene ciloleucel therapy may cross the placenta, causing foetal toxicity (including B-cell lymphocytopenia). Pregnancy following the use of axicabtagene ciloleucel should be discussed with the treating physician.
Assessment of immunoglobulin levels and B-cells in newborns of mothers treated with axicabtagene ciloleucel should be considered.
Lactation
Use axicabtagene ciloleucel with caution during breastfeeding.
The manufacturer states that breastfeeding women should be advised of the potential risk to the breast-fed infant. At the time of writing it is not known if axicabtagene ciloleucel is excreted in human breast milk. The manufacturer states that breastfeeding women should be advised of the potential risk to the breast-fed infant.
Side Effects
Abdominal pain
Alanine aminotransferase increased
Anaemia
Anxiety
Aphasia
Arrhythmias
Arthralgia
Aspartate aminotransferase increased
Ataxia
Back pain
Bacterial infection
Capillary leak syndrome
Cardiac arrest
Cardiac failure
Chills
Coagulation disorders
Constipation
Cough
Cytokine release syndrome
Decreased appetite
Dehydration
Delirium
Diarrhoea
Dizziness
Dry mouth
Dysphagia
Dyspnoea
Encephalopathy
Fatigue
Fungal infection
Headache
Histiocytosis haematophagic
Hypersensitivity reactions
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hypogammaglobulinaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Hypoxia
Insomnia
Leukopenia
Motor disturbances
Muscle pain
Myelitis
Myoclonus
Nausea
Neuropathy
Neutropenia
Oedema
Painful extremities
Pleural effusion
Pulmonary oedema
Pyrexia
Quadriplegia
Rash
Renal impairment
Seizures
Serum bilirubin increased
Spinal cord oedema
Tachycardia
Thrombocytopenia
Thrombosis
Tremor
Viral infection
Vomiting
Weight loss
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2022
Reference Sources
Summary of Product Characteristics: Yescarta 0.4 - 2 x 10 to the power of 8 cells dispersion for infusion. Gilead Sciences Ltd. Revised March 2022.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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