Posology : מינונים

4.2   Posology and method of administration

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, 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 x 106 CAR-positive viable T cells within a range of 260 to 500 x 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/day intravenously (IV) and fludarabine 30 mg/m2/day 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, 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.