ABECMA Dispersion for infusion Ref.[49954] Active ingredients: Idecabtagene vicleucel

Abecma must be administered in a qualified treatment centre.

Abecma therapy should be initiated under the direction of and supervised by a healthcare professional experienced in the treatment of haematological malignancies and trained for the administration and management of patients treated with Abecma.

A minimum of one dose of tocilizumab for use in the event of cytokine release syndrome (CRS) and emergency equipment must be available prior to infusion of Abecma. The 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

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

Treatment consists of a single dose for infusion containing a dispersion of CAR-positive viable T cells in one or more infusion bags. The target dose is 420 × 10⁶ CAR-positive viable T cells within a range of 260 to 500 × 10⁶ CAR-positive viable T cells. See the accompanying release for infusion certificate (RfIC) for additional information pertaining to dose.

Pre-treatment (lymphodepleting chemotherapy)

Lymphodepleting chemotherapy consisting of cyclophosphamide 300 mg/m² intravenously (IV) and fludarabine 30 mg/m² IV should be administered for 3 days. See the prescribing information for cyclophosphamide and fludarabine for information on dose adjustment in renal impairment.

Abecma is to be administered 2 days after completion of lymphodepleting chemotherapy, up to a maximum of 9 days. The availability of Abecma must be confirmed prior to starting the lymphodepleting chemotherapy. If there is a delay in Abecma infusion of more than 9 days, then the patient should be re-treated with lymphodepleting chemotherapy after a minimum of 4 weeks from last lymphodepleting chemotherapy prior to receiving Abecma.

Pre-medication

It is recommended that premedication with paracetamol (500 to 1,000 mg orally) and diphenhydramine (12.5 mg IV or 25 to 50 mg orally) or another H₁-antihistamine, be administered approximately 30 to 60 minutes before the infusion of Abecma to reduce the possibility of an infusion reaction.

Prophylactic use of systemic corticosteroids should be avoided as the use may interfere with the activity of Abecma. Therapeutic doses of corticosteroids should be avoided 72 hours prior to the start of lymphodepleting chemotherapy and following Abecma infusion except for the management of CRS, neurologic toxicities and other life-threatening emergencies (see section 4.4).

Clinical assessment prior to infusion

Abecma treatment should be delayed in some patient groups at risk (see section 4.4).

Monitoring after infusion

• Patients should be monitored for the first 10 days following infusion at the qualified treatment centre for signs and symptoms of CRS, neurologic events and other toxicities.
• After the first 10 days following infusion, the patient should be monitored at the physician’s discretion.
• Patients should be instructed to remain within proximity (within 2 hours of travel) of the qualified treatment centre 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. Screening for HBV, active HIV and active HCV must be performed before collection of cells for manufacturing. Leukapheresis material from patients with active HIV or active HCV infection will not be accepted for Abecma manufacturing (see section 4.4).

Elderly

No dose adjustment is required in patients over 65 years of age (see section 5.1).

Paediatric population

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

Method of administration

Abecma is for intravenous use only.

Administration:

• Do NOT use a leukodepleting filter.
• Ensure that tocilizumab or suitable alternatives, in the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, and emergency equipment are available prior to infusion and during the recovery period.
• Central venous access may be utilised for the infusion of Abecma and is encouraged in patients with poor peripheral access.
• Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Abecma infusion bag and accompanying documentation. The total number of infusion bags to be administered must also be confirmed with the patient specific information on the release for infusion certificate (RfIC) (see section 4.4).

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

There are limited data regarding overdose with Abecma.

1 year.

Each bag must be infused within 1 hour from start of thaw. After thawing, the volume of the product intended for infusion should be kept at room temperature (20°C – 25°C).

Abecma must be stored in the vapour phase of liquid nitrogen (≤ -130°C) and must remain frozen until the patient is ready for treatment to ensure viable 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 cryopreservation bag(s) with sealed addition tube containing 10-30 mL (50 mL bag), 30-70 mL (250 mL bag) or 55-100 mL (500 mL bag) of cell dispersion.

Each cryopreservation bag is individually packed in a metal cassette.

One individual treatment dose is comprised of one or more infusion bags of the same size and fill volume.

Precautions to be taken before handling or administering the medicinal product

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

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

Preparation prior to administration

Prior to Abecma infusion, it must be confirmed that the patient’s identity matches the patient identifiers on the Abecma cassette(s), the infusion bag(s) and the release for infusion certificate (RfIC). The Abecma infusion bag must not be removed from the cassette if the information on the patient-specific label does not match the intended patient. The company must be contacted immediately if there are any discrepancies between the labels and the patient identifiers.

If more than one infusion bag has been received for treatment, thaw each infusion bag one at a time. The timing of thaw of Abecma and infusion should be coordinated. The infusion start time should be confirmed in advance and adjusted for thaw so that Abecma is available for infusion when the patient is ready.

Thawing

• Remove the Abecma infusion bag from the cassette and inspect the infusion bag for any breaches of container integrity such as breaks or cracks before thawing. If the infusion bag appears to have been damaged or to be leaking, it should not be infused and should be disposed of according to local guidelines on handling of waste of human-derived material.
• Place the infusion bag inside a second sterile bag.
• Thaw Abecma at approximately 37°C using an approved thaw device or water bath 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. Do not wash, spin down and/or resuspend Abecma in new media prior to infusion.

Administration

• Prime the tubing of the infusion set with sodium chloride 9 mg/mL (0.9%) solution for injection prior to infusion.
• Infuse Abecma within 1 hour from start of thaw as quickly as tolerated by gravity flow.
• After the entire content of the infusion bag is infused, rinse the tubing with sodium chloride 9 mg/mL (0.9%) solution for injection at the same infusion rate to ensure all product is delivered.
• Follow the same procedure for all subsequent infusion bags for the identified patient.

Measures to take in case of accidental exposure

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

Precautions to be taken for disposal of the medicinal product

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