TECARTUS Dispersion for infusion Ref.[49724] Active ingredients: Brexucabtagene autoleucel

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. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.

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), with a 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 5^th, 4^th, and 3^rd 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 2^nd day before infusion of Tecartus. Fludarabine 25 mg/m² over 30 minutess must be administered prior to infusing Tecartus. The recommended days are on the 4^th, 3^rd, and 2^nd 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

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. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
• 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.

There are no data regarding the signs of overdose with Tecartus.

Tecartus is stable for 1 year when stored frozen in the vapour phase of liquid nitrogen (≤ −150°C).

Tecartus is stable at room temperature (20°C to 25°C) for up to 3 hours after thawing. However, Tecartus infusion must begin within 30 minutes of thaw completion and the total infusion time should not exceed 30 minutes.

Tecartus must be stored in the vapour phase of liquid nitrogen (≤ −150°C) and must remain frozen until the patient is ready for treatment to ensure viable live autologous cells are available for patient administration. Thawed product must not be refrozen.

For storage conditions after thawing of the medicinal product, see section 6.3.

Ethylene-vinyl acetate cryostorage bag with sealed addition tube and two available spike ports, containing approximately 68 mL of cell dispersion.

One cryostorage bag is individually packed in a shipping metal cassette.

Irradiation could lead to inactivation of the product.

Precautions to be taken before handling or administering the medicinal product

Tecartus must be transported within the facility in closed, break-proof, leak-proof containers.

This medicinal product contains human blood cells. Healthcare professionals handling Tecartus must take appropriate precautions (wearing gloves and eye protection) to avoid potential transmission of infectious diseases.

Preparation prior to administration

• Verify that the patient’s identity (ID) matches the patient identifiers on the Tecartus metal cassette.
• The Tecartus infusion bag must not be removed from the metal cassette if the information on the patientspecific label does not match the intended patient.
• Once the patient ID is confirmed, remove the infusion bag from the metal cassette.
• Check that the patient information on the metal cassette label matches that on the bag label.
• Inspect the infusion bag for any breaches of container integrity before thawing. If the bag is compromised, follow the local guidelines for handling of waste of humanderived material (and immediately contact Kite).

Thawing

• Place the infusion bag inside a second bag.
• Thaw Tecartus at approximately 37 °C using either a water bath or dry thaw method until there is no visible ice in the infusion bag. Gently mix the contents of the bag to disperse clumps of cellular material. If visible cell clumps remain, continue to gently mix the contents of the bag. Small clumps of cellular material should disperse with gentle manual mixing. Tecartus must not be washed, spun down, and/or re-suspended in new media prior to infusion. Thawing should take approximately 3 to 5 minutes.
• Once thawed, Tecartus is stable at room temperature (20°C – 25°C) for up to 3 hours. However, Tecartus infusion must begin within 30 minutes of thaw completion.

Administration

• For autologous single use only.
• Tocilizumab and emergency equipment must be available prior to infusion and during the monitoring period. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
• A leukodepleting filter must not be used.
• Central venous access is recommended for the administration of Tecartus.
• Verify the patient ID again to match the patient identifiers on the Tecartus bag.
• Prime the tubing with sodium chloride 9 mg/mL (0.9%) solution for injection (0.154 mmol sodium per mL) prior to infusion.
• Infuse the entire content of the Tecartus bag within 30 minutes by either gravity or a peristaltic pump.
• Gently agitate the bag during infusion to prevent cell clumping.
• After the entire content of the bag is infused, rinse the tubing at the same infusion rate with sodium chloride 9 mg/mL (0.9%) solution for injection (0.154 mmol sodium per mL) to ensure all the treatment is delivered.

Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and all material that has been in contact with Tecartus (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines on the handling of waste of human-derived material.

Accidental exposure

In case of accidental exposure to Tecartus local guidelines on handling of human-derived material must be followed. Work surfaces and materials which have potentially been in contact with Tecartus must be decontaminated with appropriate disinfectant.