YESCARTA Dispersion for infusion Ref.[8759] Active ingredients: Axicabtagene ciloleucel

Yescarta 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 the medicinal product.

In the event of cytokine release syndrome (CRS), at least 1 dose of tocilizumab, 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

Yescarta is intended for autologous use (see section 4.4).

Treatment consists of a single dose for infusion containing a dispersion for infusion of CAR-positive viable T cells in one infusion bag. The target dose is 2 × 10⁶ CAR-positive viable T cells per kg of body weight (within a range of 1 × 10⁶ – 2 × 10⁶ cells/kg), with a maximum of 2 × 10⁸ CAR-positive viable T cells for patients 100 kg and above. The availability of Yescarta must be confirmed prior to starting the lymphodepleting regimen.

Pre-treatment (lymphodepleting chemotherapy):

• A lymphodepleting chemotherapy regimen consisting of cyclophosphamide 500 mg/m² intravenously and fludarabine 30 mg/m² intravenously must be administered prior to infusing Yescarta. The recommended days are on the 5^th, 4^th, and 3^rd day before infusion of Yescarta.

Pre-medication:

• It is recommended that pre-medication with paracetamol 500-1 000 mg given orally and diphenhydramine 12.5 to 25 mg intravenously or orally, or equivalent medicinal products, be administered approximately 1 hour before the infusion of Yescarta to reduce the possibility of an infusion reaction.
• Prophylactic use of systemic corticosteroids is not recommended (see section 4.5).

Monitoring:

• Patients must be monitored daily for the first 7 days following infusion for signs and symptoms of potential CRS, neurologic events and other toxicities. Physicians can consider hospitalisation for the first 7 days or at the first signs or symptoms of CRS and/or neurologic events.
• After the first 7 days following the infusion, the patient is to be monitored at the physician’s discretion.
• Patients must remain within proximity of a qualified clinical facility for at least 4 weeks following infusion.

Special populations

Patients with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection

There is limited clinical experience in patients with active HIV, HBV or HCV infection.

Elderly

No dose adjustment is required in patients ≥ 65 years of age.

Paediatric population

The safety and efficacy of Yescarta in children and adolescents below 18 years of age have not yet been established. No data are available.

Method of administration

Yescarta is to be administered via intravenous infusion.

Yescarta must not be irradiated. A leukodepleting filter must not be used.

Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Yescarta 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.
• Yescarta is intended for autologous use only, it must be confirmed that the patient’s identity matches the patient identifiers on the Yescarta infusion bag.
• Once the tubing has been primed, the entire content of the Yescarta infusion bag must be infused within 30 minutes by either gravity or a peristaltic pump.

For detailed instructions on preparation, administration, measures to take in case of accidental exposure and disposal of Yescarta, see section 6.6.

No data from clinical studies are available regarding overdose of Yescarta.

1 year.

28 The stability of Yescarta upon completion of thawing is up to 3 hours at room temperature (20°C to 25°C). However, Yescarta infusion must begin within 30 minutes of thaw completion and the total infusion time should not exceed 30 minutes.

Yescarta 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 medicinal product should 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 cassette.

Irradiation could lead to inactivation of the product.

Precautions to be taken before handling or administering the medicinal product

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

This medicinal product contains human blood cells. Healthcare professionals handling Yescarta 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 Yescarta cassette.
• The Yescarta infusion bag must not be removed from the metal cassette if the information on the patient-specific label does not match the intended patient.
• Once the patient ID is confirmed, remove the Yescarta infusion bag from the metal cassette.
• Check that the patient information on the metal cassette label matches that on the infusion bag label.
• Inspect the infusion bag for any breaches of container integrity before thawing. If the infusion bag is compromised, follow the local guidelines for the handling of waste of human-derived material (or immediately contact Kite).

Thawing

• Place the infusion bag inside a second bag.
• Thaw Yescarta 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 infusion bag to disperse clumps of cellular material. If visible cell clumps remain, continue to gently mix the contents of the infusion bag. Small clumps of cellular material should disperse with gentle manual mixing. Yescarta must not be washed, spun down, and/or re-suspended in new medium prior to infusion. Thawing takes approximately 3 to 5 minutes.
• Once thawed, Yescarta is stable at room temperature (20°C-25°C) for up to 3 hours. However, Yescarta infusion must begin within 30 minutes of thaw completion.

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.
• Yescarta is for autologous use only.
• The patient’s identity must be matched with the patient identifiers on the Yescarta infusion bag.
• Central venous access is recommended for the administration of Yescarta.
• The tubing must be primed with sterile sodium chloride 9 mg/mL (0.9%) (0.154 mmol sodium per mL) solution for injection prior to infusion.
• The entire content of the Yescarta infusion bag must be infused within 30 minutes by either gravity or a peristaltic pump.
• Gently agitate the infusion bag during Yescarta infusion to prevent cell clumping.
• After the entire content of the infusion bag is infused, the infusion bag and the tubing must be rinsed at the same infusion rate with 10 to 30 mL sodium chloride 9 mg/mL (0.9%) solution for injection by back priming to ensure all Yescarta is delivered.

Measures to take in case of accidental exposure

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

Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and all material that has been in contact with Yescarta (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.