Autologous anti-cd19-transduced cd3+ cells parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions of autologous anti-CD19-transduced CD3+ cells.
Drugs List
Therapeutic Indications
Uses
Relapsed or refractory mantle cell lymphoma
Adults with relapsed or refractory mantle cell lymphoma (MCL) after two or more lines of systemic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
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 infusion of autologous anti-CD19-transduced CD3+ cells.
Pre-medication
500mg to 1g paracetamol (oral) and 12.5mg to 25mg diphenhydramine (intravenous or oral) should be administered approximately 1 hour before autologous anti-CD19-transduced CD3+ cells infusion.
Anti-CD19-transduced CD3+ cells infusion
A dose of anti-CD19-transduced CD3+ cells contains 2 million CAR-positive viable T cells per kg of bodyweight, or a maximum of 200 million cells for patients 100kg and above.
Additional Dosage Information
Management of cytokine release syndrome (CRS)
Grade 1
Tocilizumab: If not improving after 24 hours, administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum of 800mg.
Steroids: No action needed.
Grade 2
Tocilizumab: Administer 8mg/kg tocilizumab intravenously over 1 hour, up to a maximum of 800mg. 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 of 800mg. 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 or equivalent dexamethasone (10mg intravenously every 6 hours) until grade 1, then taper corticosteroids. 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 of 800mg. 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, taper corticosteroids and 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 until neurologic reactions resolve to grade 1 or lower, taper corticosteroids.
Grade 3
Consider non-sedating anti-seizure medication for seizure prophylaxis (e.g levetiracetam). Administer 10mg dexamethasone intravenously every 6 hours until neurologic reactions resolve to grade 1 or lower, taper corticosteroids. If neurologic adverse reactions do not improve, manage as per grade 4.
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. If neurologic adverse reactions do not improve, consider alternative immunosuppressants.
With concurrent cytokine release syndrome (CRS)
Grade 1
No action needed.
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 of 800mg. 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 alongside the first dose of tocilizumab and repeat every 6 hours (if not already taking other corticosteroids). Continue dexamethasone until neurologic adverse events resolve to grade 1 or less, then taper corticosteroids. If neurologic adverse reactions improve, discontinue tocilizumab. If neurologic adverse reactions do not improve, manage as per grade 3.
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 of 800mg. 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 dose every 6 hours (if not already taking other corticosteroids). Continue dexamethasone until neurologic adverse events resolve to grade 1 or less, then taper corticosteroids. If neurologic adverse reactions improve, discontinue tocilizumab and manage as per grade 2. If neurologic adverse reactions do not improve, manage as per grade 4.
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 of 800mg. 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 neurologic adverse reactions improve, manage as per grade 3. If neurologic adverse reactions do not improve, consider alternative immunosuppressants.
Administration
Autologous anti-CD19-transduced CD3+ cells should be prepared according to the manufacturer's instructions and using appropriate precautions. It should then be administered by intravenous infusion.
Autologous anti-CD19-transduced CD3+ cells is strictly for autologous use only.
Contraindications
Children under 18 years
Graft-versus-host-disease
Uncontrolled systemic infection
Within 6 weeks of live vaccines
Hepatitis B
Hepatitis C
Positive HIV status
Pregnancy
Severe cardiac disorder
Severe hypotension
Severe pulmonary disease
Precautions and Warnings
Restricted sodium intake
Breastfeeding
Cardiac impairment
Central nervous system disorder
CNS leukaemia or lymphoma
Dehydration
Hepatic impairment
History of central nervous system disorder
Renal impairment
Avoid live vaccines during treatment and until immune recovery
Before initiating treatment screen all patients for HBV, HCV and HIV
Consider anti-infective prophylaxis in immunocompromised patients
Cytokine release syndrome may require immunosuppressive treatment
Sodium content of formulation may be significant
Advise patient not to drive/operate machinery for 8 weeks after treatment
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
Premedicate with an antihistamine and paracetamol
Treatment to be initiated and supervised by a specialist
Contains dimethyl sulfoxide (DMSO)
May contain trace amounts of gentamicin
Administer by IV infusion over 30 minutes
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 for and manage hepatitis reactivation during treatment
Monitor for hypogammaglobulinaemia and manage accordingly
Monitor for signs of cytokine release syndrome daily, for at least 10 days
Monitor for signs of neurological toxicity
Monitor full blood count regularly
Monitor patient for signs of serious infection
Monitor patients for development of second primary malignancies
Monitor patients for signs of tumour lysis syndrome
Consider cardiac telemetry/pulse oximetry if CRS/neurologic reaction occurs
Risk of developing opportunistic infections
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 autologous anti-CD19-transduced CD3+ cells activity, and as such is not recommended.
Gloves and glasses should be worn to avoid the transmission of infectious blood-borne diseases.
As autologous anti-CD19-transduced CD3+ cells 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.
Cytokine release syndrome (CRS) and neurologic adverse events are common observed reactions to autologous anti-CD19-transduced CD3+ cells 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 autologous anti-CD19-transduced CD3+ cells 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.
Pregnancy and Lactation
Pregnancy
Autologous anti-CD19-transduced CD3+ cells is contraindicated during pregnancy.
The manufacturer contraindicates the use of autologous anti-CD19-transduced CD3+ cells in pregnancy. At the time of writing there is no available data of the use of autologous anti-CD19-transduced CD3+ cells during pregnancy. Based on the mechanism of action, there is a theoretical risk that if transduced cells cross the placenta, they may cause foetal toxicity (including B-cell lymphocytopenia).
Lactation
Use autologous anti-CD19-transduced CD3+ cells 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 autologous anti-CD19-transduced CD3+ cells 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
Acute renal insufficiency
Alanine aminotransferase increased
Anaemia
Anxiety
Aphasia
Arrhythmias
Aspartate aminotransferase increased
Ataxia
Bacterial infection
Bradycardia
Chills
Coagulation disorders
Constipation
Cough
Cytokine release syndrome
Decreased appetite
Dehydration
Delirium
Diarrhoea
Dizziness
Dry mouth
Dysphagia
Dyspnoea
Encephalopathy
Fatigue
Fungal infection
Haemorrhage
Headache
Hypertension
Hypoalbuminaemia
Hypocalcaemia
Hypogammaglobulinaemia
Hypokalaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Hypoxia
Increased uric acid level
Infections
Insomnia
Leukopenia
Lymphopenia
Motor disturbances
Musculoskeletal pain
Nausea
Neuropathy
Neutropenia
Oedema
Oliguria
Oral pain
Pain
Pleural effusion
Pulmonary oedema
Pyrexia
Raised intracranial pressure
Rash
Respiratory failure
Seizures
Tachycardia
Thrombocytopenia
Thrombosis
Tremor
Viral infection
Vomiting
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: June 2021
Reference Sources
Summary of Product Characteristics: Tecartus cells dispersion for infusion. Gilead Sciences Ltd. Revised January 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.