- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusions of tisagenlecleucel.
Large B-cell lymphoma
Leukaemia - acute lymphoblastic
Paediatric and young adults up to and including 25 years with B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse.
Adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.
Whilst the typical dose stated below is given as recommended by the manufacturer, local cancer network protocols and product literature should also be consulted.
Pre-treatment (lymphodepleting chemotherapy)
B-cell ALL 30mg fludarabine per metre squared (intravenous) daily for 4 days and 500mg cyclophosphamide per metre squared (intravenous) daily for 2 days starting with the first dose of fludarabine.
If Grade 4 haemorrhagic cystitis occurs with cyclophosphamide or demonstrated a chemorefractory state to a cyclophosphamide-containing regimen prior to lymphodepleting chemotherapy, then the following pre-treatment should be used: 500mg cytarabine per metre squared (intravenous) daily for 2 days and 150mg etoposide per metre squared (intravenous) daily for 3 days starting with the first dose of cytarabine.
DLBCL 25mg fludarabine per metre squared (intravenous) daily for 3 days and 250mg cyclophosphamide per metre squared (intravenous) daily for 3 days starting with the first dose of fludarabine.
If Grade 4 haemorrhagic cystitis occurs with cyclophosphamide or demonstrated a chemorefractory state to a cyclophosphamide-containing regimen prior to lymphodepleting chemotherapy, then the following pre-treatment should be used: 90mg bendamustine per metre squared (intravenous) daily for 2 days. Lymphodepleting chemotherapy may be omitted if the patientâ€?s white blood cell count is less than or equal to 1000 cells per microlitre within 1 week prior to tisagenlecleucel infusion.
Pre-medication Paracetamol and diphenhydramine should be administered approximately 30 minutes to 1 hour before tisagenlecleucel infusion.
B-cell ALL patients Patients 50kg and below: 0.2 to 5 x 10 to the power of 6 CAR-positive viable T cells per kg of bodyweight. Patients above 50kg: 0.1 to 2.5 x 10 to the power of 8 CAR-positive viable T cells. DLBCL patients 0.6 to 6 x 10 to the power of 8 CAR-positive viable T cells.
Pre-treatment (lymphodepleting chemotherapy)
(See Dosage; Adult)
B-cell ALL patients
Children aged 3 to 18: (See Dosage; Adult)
Tisagenlecleucel should be prepared according to the manufacturer's instructions and using appropriate precautions. It should then be administered by intravenous infusion centrally. If the volume of tisagenlecleucel is less than or equal to 20mL, intravenous push may be used as an alternative method of administration.
Tisagenlecleucel is strictly for autologous use only.
Children under 3 years
Uncontrolled systemic infection
Within 4 months of stem cell transplant
Within 6 weeks of live vaccines
Positive HIV status
Severe cardiac disorder
Severe pulmonary disease
Precautions and Warnings
Children under 18 years
Patients over 65 years
Restricted sodium intake
CNS leukaemia or lymphoma
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
Pre-medicate with antihistamines with or without antipyretics
Treatment to be initiated and supervised by a specialist
Contains dimethyl sulfoxide (DMSO)
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 signs of cytokine release syndrome daily, for at least 10 days
Monitor for signs of neurological toxicity
Monitor patient for signs of serious infection
Monitor patients for development of second primary malignancies
Monitor patients for signs of tumour lysis syndrome
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Antibodies to ingredient may develop
May lead to false positive HIV test result in non-infected individuals
Advise patient to seek advice at first indications of pregnancy
Not licensed for all indications in all age groups
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 tisagenlecleucel activity, and as such is not recommended. Gloves and glasses should be worn to avoid the transmission of infectious blood-borne diseases. As tisagenlecleucel 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. Febrile neutropenia may be concurrent with CRS, and should be managed with broad spectrum antibiotics, fluids and other supportive care. Ensure tocilizumab is available for each patient prior to infusing tisagenlecleucel for use in the event of cytokine release syndrome. The treatment centre must have access to additional doses of tocilizumab within 8 hours. The risk/benefit of tisagenlecleucel in patients with active CNS leukaemia and active CNS lymphoma has not been established.
Pregnancy and Lactation
Tisagenlecleucel is contraindicated during pregnancy. The manufacturer contraindicates the use of tisagenlecleucel in pregnancy. At the time of writing there is no information regarding the use of tisagenlecleucel during pregnancy. It is not known whether tisagenlecleucel crosses the placenta so the potential to cause foetal toxicity (including B-cell lymphocytopenia) is unknown.
Use tisagenlecleucel 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 tisagenlecleucel is excreted in human breast milk. The manufacturer states that breastfeeding women should be advised of the potential risk to the breast-fed infant.
Acute kidney injury
Alanine aminotransferase increased
Aspartate aminotransferase increased
Capillary leak syndrome
Changes of blood pressure
Cytokine release syndrome
Graft versus host disease
Increase in alkaline phosphatase
Increased partial thromboplastin time
Increased serum ferritin
Intravascular coagulation (disseminated)
Pain - generalised
Prothrombin time increased
Reduced lymphocyte count
Reduced neutrophil count
Reduced platelet count
Reduction of fibrinogen
Serum bilirubin increased
Tumour lysis syndrome
White blood cell count decreased
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 ).
Last Full Review Date: March 2020
Summary of Product Characteristics: Kymriah cells dispersion for infusion. Novartis Pharmaceuticals Ltd. Revised March 2020.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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