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

YESCARTA must be administered in a qualified clinical setting.

YESCARTA therapy should be initiated under the direction of and supervised by a healthcare professional experienced in the treatment of haematological malignancies and trained for administration and management of patients treated with YESCARTA. A minimum of four doses of tocilizumab for use in the event of cytokine release syndrome (CRS) and emergency equipment must be available prior to infusion of YESCARTA.

Posology

YESCARTA is intended for autologous use only (see section 4.4).

A single dose of YESCARTA contains 2 × 10⁶ CAR-positive viable T cells per kg of body weight (or maximum of 2 × 10⁸ CAR-positive viable T cells for patients 100 kg and above) in approximately 68 mL dispersion in an infusion bag.

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 intravenous and fludarabine 30 mg/m² intravenous should be administered on the 5^th, 4^th, and 3^rd day before infusion of YESCARTA.

Pre-medication

• Paracetamol 500-1,000 mg given orally and diphenhydramine 12.5 to 25 mg intravenous or oral (or equivalent) approximately 1 hour before YESCARTA infusion is recommended.
• Prophylactic use of systemic corticosteroids is not recommended as it may interfere with the activity of YESCARTA.

Monitoring

• Patients should 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 or symptoms of CRS and/or neurologic events.
• After the first 10 days following the infusion, the patient should be monitored at the physician’s discretion.
• Patients should be instructed to 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 no clinical experience in patients with active HIV, HBV or HCV infection.

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.

Elderly

No dose adjustment is required in patients ≥65 years of age. Efficacy was consistent with the overall treated patient population.

Method of administration

YESCARTA is to be administered via intravenous infusion.

YESCARTA must not be irradiated. Do NOT use a leukodepleting filter.

Precautions to be taken before handling or administering the medicinal product

This medicinal product contains genetically modified human blood cells. Healthcare professionals handling YESCARTA should take appropriate precautions (wearing gloves and glasses) to avoid potential transmission of infectious diseases.

Preparation of YESCARTA

• Verify that the patient’s identity (ID) matches the patient identifiers on the YESCARTA cassette.
• The YESCARTA bag must not be removed from the cassette if the information on the patient- specific label does not match the intended patient.
• Once the patient ID is confirmed, remove the YESCARTA bag from the cassette.
• Check that the patient information on the cassette label matches that on the bag label.
• Inspect the product bag for any breaches of container integrity before thawing. If the bag is compromised, follow the local guidelines (or immediately contact Kite).
• Place the infusion bag inside a second sterile bag or per local guidelines.
• 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 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. YESCARTA should 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, YESCARTA is stable at room temperature (20°C-25°C) for up to 3 hours.

Administration

• For autologous use only.
• Tocilizumab and emergency equipment should be available prior to infusion and during the monitoring period.
• A leukodepleting filter must not be used.
• Central venous access is recommended for the administration of YESCARTA.
• Verify the patient ID again to match the patient identifiers on the YESCARTA bag.
• Prime the tubing with 0.9% sodium chloride solution (0.154 mmol sodium per mL) prior to infusion.
• Infuse the entire content of the YESCARTA bag within 30 minutes by either gravity or a peristaltic pump. YESCARTA is stable at room temperature for up to 3 hours after thaw.
• Gently agitate the bag during YESCARTA infusion to prevent cell clumping.
• After the entire content of the bag is infused, rinse the tubing at the same infusion rate with 0.9% sodium chloride solution (0.154 mmol sodium per mL) to ensure all YESCARTA is delivered.

For special precautions for disposal, see section 6.6.

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

Shelf life

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

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

YESCARTA bags must be stored in the vapour phase of liquid nitrogen (≤ -150°C) and YESCARTA must remain frozen until the patient is ready for treatment to ensure viable live autologous cells are administered to the patient.

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 for the disposal of the medicinal product

YESCARTA contains genetically modified human blood cells. Local biosafety guidelines should be followed for unused medicinal products or waste material. All material that has been in contact with YESCARTA (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local biosafety guidelines.