Drugs List

Therapeutic Indications

Uses

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.

Administration

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.

Contraindications

Children under 3 years
Graft-versus-host-disease
Uncontrolled systemic infection
Within 4 months of stem cell transplant
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

Children under 18 years
Patients over 65 years
Restricted sodium intake
Breastfeeding
CNS leukaemia or lymphoma
Dehydration

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

Pregnancy

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.

Lactation

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.

Side Effects

Abdominal distension
Abdominal pain
Abnormal INR
Acute kidney injury
Alanine aminotransferase increased
Anaemia
Anxiety
Arrhythmias
Arthralgia
Ascites
Aspartate aminotransferase increased
Asthenia
Back pain
Bacterial infection
Capillary leak syndrome
Cardiac arrest
Cardiac failure
Cerebral haemorrhage
Cerebral infarct
Changes of blood pressure
Chills
Coagulation disorders
Compartment syndrome
Constipation
Cough
Cytokine release syndrome
Decreased appetite
Delirium
Diarrhoea
Dizziness
Dry mouth
Dyspnoea
Electrolyte disturbances
Encephalopathy
Epistaxis
Erythema
Fatigue
Febrile neutropenia
Fluid overload
Flushing
Fungal infection
Graft versus host disease
Headache
Histiocytosis haematophagic
Hyperbilirubinaemia
Hyperglycaemia
Hyperhidrosis
Hyperuricaemia
Hypoalbuminaemia
Hypogammaglobulinaemia
Hypoxia
Increase in alkaline phosphatase
Increased fibrin
Increased partial thromboplastin time
Increased serum ferritin
Infections
Influenza-like symptoms
Intravascular coagulation (disseminated)
Leukopenia
Lymphopenia
Mouth haemorrhage
Multiorgan failure
Myalgia
Nausea
Neuralgia
Night sweats
Oedema
Pain - generalised
Pancytopenia
Peripheral neuropathy
Petechiae
Pleural effusion
Prothrombin time increased
Pruritus
Pulmonary infiltration
Pulmonary oedema
Pyrexia
Rash
Reduced lymphocyte count
Reduced neutrophil count
Reduced platelet count
Reduction of fibrinogen
Seizures
Serum bilirubin increased
Sleep disorders
Speech disturbances
Stomatitis
Tachycardia
Tachypnoea
Thrombocytopenia
Tremor
Tumour lysis syndrome
Viral infection
Vomiting
Weight loss
White blood cell count decreased

Presentation

Infusions of tisagenlecleucel.

Drugs List

Therapeutic Indications

Uses

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.

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

Children

Administration

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.

Contraindications

Children under 3 years
Graft-versus-host-disease
Uncontrolled systemic infection
Within 4 months of stem cell transplant
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

Children under 18 years
Patients over 65 years
Restricted sodium intake
Breastfeeding
CNS leukaemia or lymphoma
Dehydration

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

Pregnancy

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.

Lactation

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.

Side Effects

Abdominal distension
Abdominal pain
Abnormal INR
Acute kidney injury
Alanine aminotransferase increased
Anaemia
Anxiety
Arrhythmias
Arthralgia
Ascites
Aspartate aminotransferase increased
Asthenia
Back pain
Bacterial infection
Capillary leak syndrome
Cardiac arrest
Cardiac failure
Cerebral haemorrhage
Cerebral infarct
Changes of blood pressure
Chills
Coagulation disorders
Compartment syndrome
Constipation
Cough
Cytokine release syndrome
Decreased appetite
Delirium
Diarrhoea
Dizziness
Dry mouth
Dyspnoea
Electrolyte disturbances
Encephalopathy
Epistaxis
Erythema
Fatigue
Febrile neutropenia
Fluid overload
Flushing
Fungal infection
Graft versus host disease
Headache
Histiocytosis haematophagic
Hyperbilirubinaemia
Hyperglycaemia
Hyperhidrosis
Hyperuricaemia
Hypoalbuminaemia
Hypogammaglobulinaemia
Hypoxia
Increase in alkaline phosphatase
Increased fibrin
Increased partial thromboplastin time
Increased serum ferritin
Infections
Influenza-like symptoms
Intravascular coagulation (disseminated)
Leukopenia
Lymphopenia
Mouth haemorrhage
Multiorgan failure
Myalgia
Nausea
Neuralgia
Night sweats
Oedema
Pain - generalised
Pancytopenia
Peripheral neuropathy
Petechiae
Pleural effusion
Prothrombin time increased
Pruritus
Pulmonary infiltration
Pulmonary oedema
Pyrexia
Rash
Reduced lymphocyte count
Reduced neutrophil count
Reduced platelet count
Reduction of fibrinogen
Seizures
Serum bilirubin increased
Sleep disorders
Speech disturbances
Stomatitis
Tachycardia
Tachypnoea
Thrombocytopenia
Tremor
Tumour lysis syndrome
Viral infection
Vomiting
Weight loss
White blood cell count decreased

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: March 2020

Reference Sources

Summary of Product Characteristics: Kymriah cells dispersion for infusion. Novartis Pharmaceuticals Ltd. Revised March 2020.