Posology : מינונים

4.2   Posology and method of administration

Tecartus must be administered in a qualified treatment centre by a physician with experience in the treatment of haematological malignancies and trained for administration and management of patients treated with Tecartus. At least 1 dose of tocilizumab for use in the event of cytokine release syndrome (CRS) and emergency equipment must be available prior to infusion. The qualified treatment centre must have access to an additional dose of tocilizumab within 8 hours of each previous dose.

Posology

Tecartus is intended for autologous use only (see section 4.4).
Mantle cell lymphoma
Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one container. The target dose is 2 × 106 CAR-positive viable T cells per kg of body weight (range: 1 × 106 – 2 × 106 cells/kg), or maximum of 2 × 108 CAR-positive viable T cells for patients 100 kg and above.

Tecartus is recommended to be infused 3 to 14 days after completion of the lymphodepleting chemotherapy for MCL patients. The availability of the treatment must be confirmed prior to starting the lymphodepleting regimen.

Pre-treatment (lymphodepleting chemotherapy) for MCL patients
•     A lymphodepleting chemotherapy regimen consisting of cyclophosphamide 500 mg/m² and fludarabine 30 mg/m² must be administered prior to infusing Tecartus. The recommended days are on the 5th, 4th, and 3rd day before infusion of Tecartus.

Acute lymphoblastic leukaemia
Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one container. The target dose is 1 × 106 CAR-positive viable T cells per kg of body weight, with a maximum of 1 × 108 CAR-positive viable T cells for patients 100 kg and above.


Tecartus is recommended to be infused 2 to 14 days after completion of the lymphodepleting chemotherapy for ALL patients. The availability of the treatment must be confirmed prior to starting the lymphodepleting regimen.

Pre-treatment (lymphodepleting chemotherapy) for ALL patients
A lymphodepleting chemotherapy regimen consisting of cyclophosphamide 900 mg/m2 over 60 minutes must be administered prior to infusing Tecartus. This is recommended on the 2nd day before infusion of Tecartus. Fludarabine 25 mg/m2 over 30 minutes must be administered prior to infusing Tecartus. The recommended days are on the 4th, 3rd, and 2nd day before infusion of Tecartus.

Mantle cell lymphoma and acute lymphoblastic leukaemia

Pre-medication
•    To minimise potential acute infusion reactions, it is recommended that patients be pre-medicated with paracetamol 500 to 1,000 mg given orally and diphenhydramine 12.5 to 25 mg intravenous or oral (or equivalent) approximately 1 hour prior to infusion.
•    Prophylactic use of systemic corticosteroids is not recommended (see section 4.5).

Monitoring prior to infusion
•    In some patient groups at risk, a delay of the Tecartus infusion may be indicated (see section 4.4- Reasons to delay treatment).

Monitoring after infusion
•    Patients must be monitored daily for the first 10 days following infusion for signs and symptoms of potential CRS, neurologic events and other toxicities. Physicians should consider hospitalisation for the first 10 days post infusion or at the first signs/symptoms of CRS and/or neurologic events.
•    After the first 10 days following the infusion, the patient is to be monitored at the physician’s discretion.
•    Patients must be instructed to remain within proximity (within 2 hours of travel) of a qualified treatment centre for at least 4 weeks following infusion.

Special populations

Elderly
No dose adjustment is required in patients ≥65 years of age.
Patients seropositive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
There is no experience with manufacturing Tecartus for patients with a positive test for HIV, active HBV, or active HCV infection. Therefore, the benefit/risk has not yet been established in this population.

Paediatric population
Tecartus is not indicated for children and adolescents under 18 years old.
The safety and efficacy of Tecartus in children and adolescents aged less than 18 years have not yet been established. No data are available.

Method of administration

Tecartus is for intravenous use only.
Tecartus must not be irradiated. Do NOT use a leukodepleting filter.

Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Tecartus infusion bag and cassette.

Administration
•    A leukodepleting filter must not be used.
•    Tocilizumab and emergency equipment must be available prior to infusion and during the monitoring period.
•    For autologous use only, verify the patient ID to match the patient identifiers on the Tecartus bag.
•    Once tubing has been primed, infuse the entire content of the Tecartus bag within 30 minutes by either gravity or a peristaltic pump.

For detailed instructions on preparation, administration, accidental exposure and disposal of Tecartus, see section 6.6.