Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: Novartis Europharm Limited, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland
Kymriah is indicated for the treatment of:
Kymriah must be administered in a qualified treatment centre. 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 Kymriah. A minimum of four doses of tocilizumab for use in the event of cytokine release syndrome and emergency equipment must be available prior to infusion.
Kymriah is intended for autologous use only (see section 4.4). Manufacture and release of Kymriah usually takes about 3-4 weeks.
Dosage in paediatric and young adult B-cell ALL patients:
Dosage in adult DLBCL patients:
Lymphodepleting chemotherapy is recommended to be administered before Kymriah infusion unless the white blood cell (WBC) count within one week prior to infusion is ≤1,000 cells/μL.
Kymriah is recommended to be infused 2 to 14 days after completion of the lymphodepleting chemotherapy. The availability of Kymriah must be confirmed prior to starting the lymphodepleting regimen. If there is a delay of more than 4 weeks between completing lymphodepleting chemotherapy and the infusion and the WBC count is >1,000 cells/μL, then the patient should be re-treated with lymphodepleting chemotherapy prior to receiving Kymriah.
The recommended lymphodepleting chemotherapy regimen is:
The recommended lymphodepleting chemotherapy regimen is:
Lymphodepleting chemotherapy may be omitted if a patient’s white blood cell (WBC) count is ≤1,000 cells/μL within 1 week prior to Kymriah infusion.
To minimise potential acute infusion reactions, it is recommended that patients be pre-medicated with paracetamol and diphenhydramine or another H1 antihistamine within approximately 30 to 60 minutes prior to Kymriah infusion. Corticosteroids should not be used at any time except in the case of a life-threatening emergency (see section 4.4).
Kymriah treatment should be delayed in some patient groups at risk (see section 4.4).
Patients should be monitored daily for the first 10 days following infusion for signs and symptoms of potential cytokine release syndrome, neurological events and other toxicities. Physicians should consider hospitalisation for the first 10 days post infusion or at the first signs/symptoms of cytokine release syndrome and/or neurological 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.
B-cell ALL: No formal studies have been performed in paediatric patients below 3 years of age.
DLBCL: The safety and efficacy of Kymriah in children and adolescents below 18 years of age have not yet been established. No data are available.
B-cell ALL: The safety and efficacy of Kymriah in this population have not been established.
DLBCL: No dose adjustment is required in patients over 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 Kymriah for patients with a positive test for active HBV, HCV or HIV. Therefore, leukapheresis material from these patients will not be accepted for Kymriah manufacturing.
Kymriah is for intravenous use only.
This medicinal product contains genetically modified human blood cells. Healthcare professionals handling Kymriah should therefore take appropriate precautions (wearing gloves and glasses) to avoid potential transmission of infectious diseases.
Prior to Kymriah infusion, it must be confirmed that the patient’s identity matches the essential unique patient information on the infusion bag(s).
The timing of thaw of Kymriah and infusion should be coordinated. Please refer to section 6.6 for details on inspection and thawing of the infusion bag. The infusion start time should be confirmed in advance and adjusted for thaw so that Kymriah is available for infusion when the recipient is ready. Once Kymriah has been thawed and is at room temperature (20°C-25°C), it should be infused within 30 minutes to maintain maximum product viability, including any interruption during the infusion.
Kymriah should be administered as an intravenous infusion through latex-free intravenous tubing without a leukocyte depleting filter, at approximately 10 to 20 mL per minute by gravity flow. All contents of the infusion bag(s) should be infused. Sodium chloride 9 mg/mL (0.9%) solution for injection should be used to prime the tubing prior to infusion and to rinse it after infusion. When the full volume of Kymriah has been infused, the infusion bag should be rinsed with 10 to 30 mL sodium chloride 9 mg/mL (0.9%) solution for injection by back priming to ensure as many cells as possible are infused into the patient.
For special precautions for disposal see section 6.6.
Not applicable.
Shelf life: 9 months.
The product should be administered immediately after thawing. After thawing, the product should be kept at room temperature (20°C-25°C) and infused within 30 minutes to maintain maximum product viability, including any interruption during the infusion.
Store and transport below -120°C, e.g. in a container for cryogenic storage (Dewar) in the vapour phase of liquid nitrogen.
Store in the original protective envelope (Tyvek) containing the cassette protecting the infusion bag.
For storage conditions after thawing of the medicinal product, see section 6.3.
Ethylene vinyl acetate (EVA) infusion bag with polyvinyl chloride (PVC) tubing and a luer spike interconnector closed by a luer-lock cap containing either 10–30 mL (50 mL bags) or 30–50 mL (250 mL bags) cell dispersion.
Each infusion bag is placed into an aluminum cassette, then put in a plastic overwrap bag with absorbent sheets and sealed in a protective envelope (Tyvek).
One individual treatment dose comprises 1 to 3 infusion bags.
Do not thaw the product until it is ready to be used.
The infusion bag should be placed inside a second, sterile bag during thawing to protect ports from contamination and avoid spills in the unlikely event of the bag leaking. Kymriah should be thawed at 37°C using either a water bath or dry thaw method until there is no visible ice in the infusion bag. The bag should be removed immediately from the thawing device and kept at room temperature (20°C-25°C) until infusion. If more than one infusion bag has been received for the treatment dose, the next bag should only be thawed after the contents of the preceding bag have been infused.
Kymriah should not be manipulated. For example, Kymriah should not be washed (spun down and resuspended in new media) prior to infusion.
The infusion bag(s) should be examined for any breaks or cracks prior to 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 biosafety procedures (see section 4.2.).
Kymriah should be transported within the facility in closed, break-proof, leak-proof containers.
Kymriah contains genetically-modified human blood cells. Local biosafety guidelines should be followed for unused medicinal product or waste material. All material that has been in contact with Kymriah (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local biosafety guidelines.
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