Source: European Medicines Agency (EU) Revision Year: 2024 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 the medicinal product.
In the event of cytokine release syndrome (CRS), at least one dose of tocilizumab and emergency equipment must be available per patient prior to infusion. The treatment centre must have access to additional doses of tocilizumab within 8 hours. 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.
Manufacture and release of Kymriah usually takes about 3-4 weeks.
Kymriah is intended for autologous use only (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 or more infusion bags.
Dose in paediatric and young adult B-cell ALL patients:
The concentration of CARpositive viable T cells is dependent on indication and patient body weight.
Dose in adult DLBCL and FL patients:
See the accompanying batch specific documentation for additional information pertaining to dose.
The availability of Kymriah must be confirmed prior to starting the lymphodepleting regimen. For B-cell ALL and DLBCL indications, Kymriah is recommended to be infused 2 to 14 days after completion of the lymphodepleting chemotherapy. For FL, Kymriah is recommended to be infused 2 to 6 days after completion of the lymphodepleting chemotherapy.
Lymphodepleting chemotherapy may be omitted if a patient is experiencing significant cytopenia, e.g., white blood cell (WBC) count ≤1 000 cells/μL within one week prior to infusion.
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:
If the patient experienced a previous Grade 4 haemorrhagic cystitis with cyclophosphamide, or demonstrated a chemorefractory state to a cyclophosphamide-containing regimen administered shortly before lymphodepleting chemotherapy, then the following should be used:
The recommended lymphodepleting chemotherapy regimen is:
If the patient experienced a previous Grade 4 haemorrhagic cystitis with cyclophosphamide, or demonstrated a chemorefractory state to a cyclophosphamide-containing regimen administered shortly before lymphodepleting chemotherapy, then the following should be used:
To minimise potential acute infusion reactions, it is recommended that patients be premedicated 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 lifethreatening emergency (see section 4.4).
Kymriah treatment should be delayed in some patient groups at risk (see section 4.4).
B-cell ALL:
The safety and efficacy of Kymriah in this population have not been established.
DLBCL and FL:
No dose adjustment is required in patients over 65 years of age.
There is no experience with manufacturing Kymriah for patients with a positive test for HIV, active HBV, or active HCV infection. Leukapheresis material from these patients will not be accepted for Kymriah manufacturing. Screening for HBV, HCV, and HIV must be performed in accordance with clinical guidelines before collection of cells for manufacturing.
B-cell ALL:
There is limited experience with Kymriah in paediatric patients below the age of 3 years. Currently available data in this age group are described in sections 4.8 and 5.1.
DLBCL:
The safety and efficacy of Kymriah in children and adolescents below 18 years of age have not yet been established. Currently available data are described in section 5.1 but no recommendation on a posology can be made.
FL:
The safety and efficacy of Kymriah in children and adolescents below 18 years of age have not yet been established. No data are available.
Kymriah is for intravenous use only.
Kymriah is intended for autologous use only. Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Kymriah infusion bags and accompanying documentation. The total number of infusion bags to be administered should also be confirmed with the patient specific information on the batch specific documentation (see section 4.4).
The timing of thaw of Kymriah and infusion should be coordinated (please refer to section 6.6).
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.
If the volume of Kymriah to be administered is ≤20 mL, intravenous push may be used as an alternative method of administration.
For detailed instructions on preparation, administration, measures to take in case of accidental exposure and disposal of Kymriah, see section 6.6.
Overdose has not been reported.
In case of overdose, the potential risk is an increased probability of developing CRS including severe CRS. For close monitoring, see section 4.2; for symptoms and management of CRS, see section 4.4.
9 months.
The medicinal 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.
Kymriah must be stored and transported ≤ -120°C, e.g. in a container for cryogenic storage in the vapour phase of liquid nitrogen, and must remain frozen until the patient is ready for treatment to ensure viable cells are available for patient administration. Do not re-freeze after thawing.
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 a protective layer.
One individual treatment dose comprises 1 or more infusion bags.
Kymriah should be transported within the facility in closed, break-proof, leak-proof containers.
This medicinal product contains human blood cells. Healthcare professionals handling Kymriah must take appropriate precautions (wearing gloves and eye protection) to avoid potential transmission of infectious diseases.
Before administration, it must be confirmed that the patient’s identity matches the unique patient information on the Kymriah infusion bags and accompanying documentation. The total number of infusion bags to be administered should also be confirmed with the patient specific information on the batch specific documentation accompanying the medicinal product.
The timing of thaw of Kymriah and infusion should be coordinated. 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.
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 (refer to the batch certificate for number of bags constituting one 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 procedures on handling of biological waste.
Kymriah intravenous infusion should be administered by a healthcare professional experienced with immunosuppressed patients and prepared to manage anaphylaxis. In the event of cytokine release syndrome (CRS), ensure that at least one dose of tocilizumab per patient and emergency equipment are available prior to infusion. Hospitals must have access to additional doses of tocilizumab within 8 hours. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, ensure that suitable alternative measures to treat cytokine release syndrome are available on site.
The patient’s identity should be matched with the patient identifiers on the infusion bag. Kymriah is intended solely for autologous use and must not, under any circumstances, be administered to other patients.
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. Sterile 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.
If the volume of Kymriah to be administered is ≤20 mL, intravenous push may be used as an alternative method of administration.
In case of accidental exposure local guidelines on handling of human-derived material should be followed. Work surfaces and materials which have potentially been in contact with Kymriah must be decontaminated with appropriate disinfectant.
Unused medicinal product and 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 guidelines on handling of human-derived material.
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