1.2 x 10 6 – 6 x 10 8 cells infusion fluid , dispersion
thisagentle nucleus (CAR + viable T cells )a
What Kymriah is and what it is used for
What Kymriah is
Kymriah, also called thisagenlekleucel, is made up of a number of your white blood cells called T cells. T cells are important for your immune system to function normally.
How does Kymriah work?
To make Kymriah, T cells are taken from your blood and a new gene is placed in the T cells so that they can target the cancer cells in your body. When you receive Kymriah via an infusion into the bloodstream, the modified T cells will find and kill the cancer cells.
What Kymriah is used for
Kymriah is used to treat:
- acute lymphoblastic B cell leukemia (B-cell ALL) – a cancer affecting certain white blood cells . It can be used in children and young adults up to the age of 25 who have this type of cancer.
- diffuse large-cell B-cell lymphoma (DLBCL) – another form of cancer that affects certain types of white blood cells , most often in the lymph nodes. It can be used in adults (from the age of 18) who have this type of cancer.
Ask your doctor if you are wondering how Kymriah works or why the medicine has been prescribed for you.
What you need to know before you are given Kymriah
You should not be given Kymriah:
- If you are allergic to any of the ingredients of this medicine (listed in section 6). Ask your doctor if you think you may be allergic.
Warnings and cautions
Kymriah is made from your white blood cells and should be given to you only.
Before you are given Kymriah, tell your doctor about:
- you have had a stem cell transplant in the last 4 months. Your doctor will check if you have any signs or symptoms of a graft ‑for ‑ host ‑ disease. This means that the transplanted cells attack your body and cause symptoms such as skin rash, nausea, vomiting, diarrhea and blood-mixed stools.
- you have problems with your lungs, heart or blood pressure (low or high).
- you notice that the symptoms of your cancer are getting worse. If you have leukemia , this may include having a fever, feeling weak, having bleeding gums or getting bruises. If you have lymphoma , it may include you getting a fever for no apparent reason, feeling weak, sweating at night or suddenly losing weight
- you have an infection . Infection one will be treated before you get Kymriah.
- you have had an infection with hepatitis B, hepatitis C or human immunodeficiency virus ( HIV ).
- you are pregnant, think you may be pregnant, or are planning to become pregnant (see sections “Pregnancy and breast-feeding” and “Contraceptives for women and men” below).
- you have been vaccinated in the last 6 weeks or are planning a vaccination in the next few months.
If any of the above apply to you (or you are not sure), talk to your doctor before taking Kymriah.
Samples and examinations
Before you are given Kymriah, your doctor will check the following:
- Lungs, heart and blood pressure .
- Signs of infection . In that case, infection one is treated before you get Kymriah.
- If your lymphoma or leukemia has worsened.
- Any signs of graft ‑about ‑ host ‑ disease, which may occur after a transplant.
- If you have uric acid in your blood and how many cancer cells you have in your blood. This shows if there is a risk that you will get so-called tumor light syndrome. You can get medicine to reduce the risk of it.
- If you have hepatitis B, hepatitis C or HIV – infection .
After you’ve got Kymriah
Tell your doctor or nurse immediately if you have any of the following:
- Fever, which can be a symptom of an infection . Your doctor will check your blood levels regularly, as the number of blood cells and other blood components may decrease.
- Measure your temperature twice a day for 3-4 weeks after administering Kymriah. Contact a doctor immediately if your temperature is elevated.
- Extreme fatigue, weakness and shortness of breath, which can be symptoms of a lack of red blood cells .
- You bleed or bruise more easily which can be a symptom of low levels of a type of blood cell in the blood called platelets .
The results of certain types of HIV tests may be affected – ask your doctor about this.
Your doctor will regularly check your blood counts after you have received Kymriah as the number of blood cells and other components in your blood may decrease.
Do not donate blood, organs, tissues, sperm, scars, or cells.
Children and young people
- No formal studies have been performed in children under 3 years of age with B-cell ALL.
- Kymriah should not be used for the treatment of DLBCL in children and adolescents under 18 years of age. Kymriah has not been studied in this age group.
Other medicines and Kymriah
Tell your doctor if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription. Other medicines may affect the way Kymriah works.
You mustn’t be given certain vaccines called live vaccines:
- for 6 weeks before you receive the short chemotherapy treatment (so-called lymphocyte- reducing chemotherapy ), which prepares your body for the Kymriah cells
- during the Kymriah treatment
- after treatment while the immune system recovers.
Talk to your doctor if you need to be vaccinated.
Before you are given Kymriah, tell your doctor or nurse if you are taking any medicines that weaken the immune system such as corticosteroids (“cortisone”). These medicines may affect the effect of Kymriah.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. The effects of Kymriah on pregnant or breastfeeding women are not known and could harm an unborn baby or a newborn baby/infant.
- If you become pregnant or think you may be pregnant after treatment with Kymriah, talk to a doctor immediately.
- Before starting treatment, a pregnancy test is performed. Kymriah should only be given if the results show that you are not pregnant.
Contraceptives for women and men
Talk to your doctor about pregnancy if you have had Kymriah.
Driving and using machines
You must not drive, use machines, or engage in any activity that requires concentration and attention as Kymriah may cause problems such as altered or impaired consciousness, confusion, and seizures for 8 weeks after infusion.
Kymriah contains sodium, dimethyl sulfoxide (DMSO) and dextran 40.
This medicine contains 24.3 to 121.5 mg of sodium per dose. This corresponds to 1 to 6% of the maximum recommended daily intake of sodium for adults. If you have not been in contact with dextran or DMSO before, you should be kept under close observation during the first minutes of the infusion period.
How to get Kymriah
Kymriah is always given by a doctor at a qualified clinic.
Kymriah contains human blood cells. The physician handling Kymriah will therefore take appropriate precautions (use gloves and goggles) to avoid the potential transmission of infectious diseases.
Donate blood for the making of Kymriah
Kymriah is made from your white blood cells.
- Your doctor will collect a quantity of your blood through a catheter that is placed in a vein. A number of your white blood cells will then be separated from your blood, the rest of the blood being returned to your vein. The procedure is called leukapheresis and can take 3 to 6 hours and may need to be repeated again.
- Your white blood cells are frozen and sent away for the production of Kymriah. It usually takes 3 to 4 weeks to make Kymriah, but the time may vary.
- Kymriah is a treatment that is made specifically for you. There may be times when the production of Kymriah is not successful and it can not be given to you. In some cases, a second attempt to make Kymriah may be made.
Before you receive Kymriah, your doctor may give you a type of treatment called lymphocyte-reducing chemotherapy for a few days to prepare your body.
Treatment of cancer while Kymriah is being manufactured
During the period of manufacture of Kymriah, your lymphoma or leukemia may worsen and your doctor may decide to use an additional treatment (a type of chemotherapy called “bridging treatment”) to stabilize your cancer by stopping the formation of new cancer cells. This treatment can lead to side effects that can be serious or life-threatening. Your doctor will inform you about the possible side effects of this treatment.
Medicines are given immediately before treatment with Kymriah
For 30-60 minutes before receiving Kymriah, you may be given other medicines to prevent infusion reactions and fever. You can get medicines such as:
- Paracetamol
- An antihistamine such as diphenhydramine.
How to give Kymriah
- Your doctor will check that the patient information on the infusion bag with Kymriah matches your information.
- The doctor will give you Kymriah as an infusion , ie. you get the drug as a drip through a tube into a vein. It usually takes less than 1 hour.
- Kymriah is a one-time treatment.
Once you’ve got Kymriah
- For at least 4 weeks after receiving Kymriah, you must plan to stay within 2 hours of travel distance from the hospital where you were treated. Your doctor will recommend that you come to the hospital daily for at least 10 days and will consider whether you need to be hospitalized for the first 10 days after infusion one. Your doctor needs to check that the treatment is working and help you if you get any side effects .
If you miss an appointment, call your doctor or hospital as soon as possible to rebook.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you get any of the following side effects after Kymriah infusion. They usually occur during the first 8 weeks after infusion but can also develop later:
Very common: may affect more than 1 in 10 people
- high fever and chills. These can be symptoms of a serious condition called cytokine release syndrome which can be life threatening or fatal. Other symptoms of cytokine release syndrome include difficulty breathing, nausea, vomiting, diarrhea, loss of appetite, fatigue, muscle aches, joint pain, swelling, low blood pressure , headache, heart, lung and kidney failure and liver damage or dizziness / fainting. These symptoms almost always occur during the first 10 days after infusion one.
- problems such as changes in thinking or decreased level of consciousness, lost perception of reality, confusion, agitation, seizures, difficulty speaking or understanding speech, difficulty walking.
- you feel hot, have a fever, chill or start shivering, have a sore throat or cold sore – this may be a sign of an infection . Some infections can be life-threatening or fatal.
Common: may affect up to 1 in 10 people
- Rapid degradation of tumor cells, which causes its contents to spread in the bloodstream. This can interfere with the function of various organs in the body, in particular the kidneys, heart and nervous system (tumor lysis syndrome)
Other possible side effects are
Other side effects are listed below. If these side effects become severe, tell your doctor immediately
Very common: may affect more than 1 in 10 people
- pale skin, weakness, shortness of breath due to low red blood cell count or low hemoglobin value
- heavy or prolonged bleeding or bruising due to low platelet count
- fever with a dangerously low white blood cell count
- increased risk of infection due to an abnormally low number of white blood cells
- frequent and persistent infection due to reduced number of antibodies in the blood
- weakness, abnormal heart rhythm, muscle spasms / cramps due to low levels of salts in the blood including phosphorus, calcium , potassium , magnesium
- high levels of liver enzyme or creatinine in the blood indicating that the liver or kidneys are not functioning normally
- anxiety, irritability
- fast or irregular heartbeat
- high blood pressure
- shortness of breath, labored breathing, increased respiratory rate, fluid in the lungs
- cough
- abdominal pain, constipation
- rash
- difficulty sleeping
- swollen ankles, arms, legs and face
Common: may affect up to 1 in 10 people
- fever, malaise, enlarged liver, yellow skin or eyes, low blood cell count due to severe immune activation
- dizziness or fainting, redness , rash, itching , fever, shortness of breath or vomiting, abdominal pain, diarrhea due to a reaction to infusion .
- rash, nausea, vomiting, diarrhea including bloody stools (possible symptoms of graft- versus-host disease which is when transplanted cells attack your cells)
- joint pain due to high levels of uric acid
- abnormal results on blood tests (high levels of phosphorus, potassium , calcium , magnesium and sodium , an enzyme called alkaline phosphatase that helps detect liver disease, fibrin d-dimer, serum ferritin , low levels of: a protein in the blood called albumin, sodium )
- convulsions, seizures
- involuntary or uncontrollable movements
- tingling or numbness, difficulty moving due to nerve damage
- visual impairment
- thirst
- weight loss
- nerve pain
- shortness of breath, difficulty lying in a supine position, swollen feet or legs (possible symptoms of heart failure ), cardiac arrest
- swelling and pain due to blood clots
- swelling due to leakage of fluid from blood vessels to surrounding tissue .
- bloating and discomfort (distended abdomen) due to an accumulation of fluid in the abdomen
- dry mouth , pain in the mouth, bleeding in the mouth, inflammation of the gums
- yellow skin and yellow eyes due to abnormally high levels of bilirubin in the blood
- itching
- heavy sweating, night sweats
- leg and back pain
- flu-like illness
- multiple organ failure
Uncommon: (may affect up to 1 in 100 people)
- weakness or paralysis of the arms or legs or of the face, speech difficulties (possible symptoms of stroke as a result of reduced blood supply)
- hot skin or sudden redness
- mucus cough or sometimes bloody cough, fever, cough that produces mucus or sometimes blood, fever, shortness of breath or difficulty breathing
How to store Kymriah
The following information is for physicians only.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the infusion bag label after EXP. The expiration date is the last day of the specified month.
Store and transport below ‑120 ° C. Do not thaw the product until it is ready to use.
Do not use this medicine if the infusion bag is damaged or leaking.
This medicine contains genetically modified blood cells. Local guidelines for the management of biological waste must be followed for unused medicines and waste.
Contents of the pack and other information
Content declaration
- The active substance in Kymriah is thisagenlekleucel. Each Kymriah infusion bag contains thisagen leucleucle cell dispersion with a batch-dependent concentration of autologous T cells that have been genetically modified to express a chimeric antigen receptor (CAR) directed against CD19 (CAR-positive viable T cells ). 1 or more bags containing a total of 1.2 X 10 6 – 6 x 10 8 CAR + viable T cell s
- The other ingredients are: glucose , sodium chloride, human albumin solution, dextran 40 for injection , dimethylsulfoxide, sodium gluconate, sodium acetate, potassium chloride, magnesium chloride, sodium- N-acetyltryptophan, sodium caprylate, aluminum and water for injections. See section 2, “Kymriah contains sodium , dimethyl sulfoxide (DMSO) and dextran 40”.
What the medicine looks like and contents of the pack
Kymriah is a cell dispersion for infusion. It is supplied in an infusion bag containing a cloudy to clear, colorless to light yellow dispersion of cells. Each bag contains 10 ml to 50 ml of dispersion.
Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland
Manufacturer
Novartis Pharma GmbH
Roonstrasse 25
90429 Nuremberg
Germany
CELLFORCURE
ZA de Courtabœuf
11 avenue des Tropiques
91940 Les Ulis
France
Contact the representative of the marketing authorization holder to find out more about this medicine:
| Belgium / Belgique / BelgienNovartis Pharma NVTel: +32 2 246 16 11 | LithuaniaSIA Novartis Baltics Lithuanian branchesTel: +370 5 269 16 50 |
| BulgariaNovartis Bulgaria EOODTel: +359 2 489 98 28 | Luxembourg / LuxemburgNovartis Pharma NVTel: +32 2 246 16 11 |
| Czech RepublicNovartis sroTel: +420 225 775 111 | HungaryNovartis Hungary Kft.Tel .: +36 1 457 65 00 |
| DenmarkNovartis Healthcare A / STel: +45 39 16 84 00 | MaltaNovartis Pharma Services Inc.Tel: +356 2122 2872 |
| GermanyNovartis Pharma GmbHTel: +49 911 273 0 | The NetherlandsNovartis Pharma BVTel: +31 88 04 52 |
| EestiSIA Novartis Baltics Eesti subsidiaryTel: +372 66 30 810 | NorwayNovartis Norge ASTel: +47 23 05 20 00 |
| GreeceNovartis (Hellas) AEBE:Ηλ: +30 210 281 17 12 | AustriaNovartis Pharma GmbHTel: +43 1 86 6570 |
| SpainNovartis Pharmacéutica, SATel: +34 93 306 42 00 | PolandNovartis Poland Sp. z ooTel .: +48 22 375 4888 |
| FranceNovartis Pharma SASTel: +33 1 55 47 66 00 | PortugalNovartis Farma – Pharmaceutical Products, SATel: +351 21 000 8600 |
| CroatiaNovartis Hrvatska dooTel. +385 1 6274 220 | RomaniaNovartis Pharma Services Romania SRLTel: +40 21 31299 01 |
| IrelandNovartis Ireland LimitedTel: +353 1 260 12 55 | SloveniaNovartis Pharma Services Inc.Tel: +386 1 300 75 50 |
| IcelandVistor hf.Phone: +354 535 7000 | Slovak RepublicNovartis Slovakia sroTel: +421 2 5542 5439 |
| ItalyNovartis Farma SpATel: +39 02 96 54 1 | Finland / FinlandNovartis Finland OyPuh / Tel: +358 (0) 10 6133 200 |
| .ΠροςNovartis Pharma Services Inc.:Ηλ: +357 22 690 690 | SwedenNovartis Sverige ABTel: +46 8 732 32 00 |
| LatviaSIA Novartis BalticsTel: +371 67 887 070 | United KingdomNovartis Pharmaceuticals UK Ltd.Tel: +44 1276 698370 |