InfoCons Consumer Protection informs you – Kymriah – Package Leaflet

Before anything else

Read all of this leaflet carefully before you (or your child) are given this medicine because it contains important information.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor.
• Your doctor will give you a Patient Alert Card. Read it carefully and follow the instructions on it.
• Always show the Patient Alert Card to the doctor or nurse when you see them or if you go to hospital.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.
• The information in this leaflet is for you or your child – but in the leaflet it will just say “you”.

ℹ️ 1. What Kymriah is and what it is used for

What Kymriah is Kymriah , also known as tisagenlecleucel, is made from some of your own white blood cells called T cells. T cells are important for your immune system (the body’s defences) to work properly.

How does Kymriah work?

The T cells are taken from your blood and a new gene is put into the T cells so that they can target the cancer cells in your body . When Kymriah is infused into your blood, the modified T cells will find and kill the cancer cells.

What Kymriah is used for

Kymriah is used to treat:

• B-cell acute lymphoblastic leukaemia (B -cell ALL) – a form of cancer that affects some other types of white blood cells. The medicine can be used in children and young adults up to and including 25 years of age with this cancer when it did not respond to previous treatment, has come back two or more times, or has come back after a transplant of stem cells.
• Diffuse large B -cell lymphoma (DLBCL) – a form of cancer that affects some types of white blood cells, mostly in the lymph nodes. The medicine can be used in adults (18 years of age or older) with this cancer when it has come back or did not respond after two or more previous treatments .
• Follicular lymphoma (FL) – a form of cancer that affects some types of white blood cells, called lymphocytes, mostly in the lymph nodes. The medicine can be used in adults (18 years of age or older) with this cancer when it has come back or did not respond after two or more previous treatments .

If you have any questions about how Kymriah works or why this medicine has been prescribed for 44 you, ask your doctor.

⚠️ 2. 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). If you think you may be allergic, ask your doctor for advice.
• If you cannot receive treatment, called lymphodepleting chemotherapy, which reduces the number of white blood cells in your blood.

Warnings and precautions

Kymriah is made from your own white blood cells and should only be given to you.

Patients treated with Kymriah may develop new types of cancers. There have been reports of patients developing cancer, beginning in a type of white blood cells called T -cells, after treatment with Kymriah and similar medicines. Talk to your doctor if you e xperience any new swelling of your glands (lymph nodes) or changes in your skin such as new rashes or lumps.

You will be asked to enrol in a registry for at least 15 years in order to better understand the long -term effects of Kymriah .

Before you are given Kymriah you should tell your doctor if:

• You have had a stem cell transplant in the last 4 months. Your doctor will check if you have signs or symptoms of graft -versus -host disease. This happens when transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhoea and bloody stools.
• You have any lung, heart or blood pressure (low or raised) problems.
• You notice the symptoms of your cancer are getting worse . If you have leukaemia this might include fever, feeling weak, bleeding gums, bruising. If you have lymphoma, this might include unexplained fever, feeling weak, night sweats, sudden weight loss.
• You have an infection. The infection will be treated before the Kymriah infusion.
• You have had hepatitis B, hepatitis C or human immunodeficiency virus ( HIV) infection .
• You are pregnant, think you may be pregnant, or plan to become pregnant (see sections “Pregnancy and breast -feeding ” and “Contraception for women and men ” below).
• You had a vaccination in the previous 6 weeks or are planning to have one in the next few months.

If any of the above apply to you (or you are not sure), talk to your doctor before being given Kymriah.

Test and checks Before you are given Kymriah your doctor will:

• Check your lungs, heart and blood pressure.
• Look for signs of infection; any infection will be treated before you are given Kymriah.
• Check if your lymphoma or leuk aemia is getting worse.
• Look for signs of graft-versus -host disease that can happen after a transplant.
• Check your blood for uric acid and for how many cancer cells there are in your blood. This will show if you are likely to develop a condition called tumour lysis syndrome. You may be given medicines to help prevent the condition .
• Check for hepatitis B, hepatitis C or HIV infection .

45 After you have been given Kymriah Tell your doctor or nurse immediately if you have any of the following :

• Fever, which may be a symptom of an infection. Your doctor will regularly check your blood counts as the number of blood cells and other blood components may decrease .
• Take your temperature twice a day for 3 -4 weeks after treatment with Kymriah. If your temperature is high, see your doctor immediately.
• Altered or decreased consciousness, delirium, anxiety, dizziness, tremor, headache, confusion, agitation, seizures, difficulty speaking and understanding, and /or loss of balance. This is usually within the first 8 weeks after the infusion, but it can be after too. These may be symptoms of a condition called immune effector cell -associated neurotoxicity syndrome (ICANS).
• Extreme tiredness, weakness and shortness of breath, which may be symptoms of a lack of red blood cells.
• Bleeding or bruising more easily, which may be symptoms of low levels of cells in the blood known as platelets.

There may be an effect on the results of some types of HIV test – ask your doctor about this.

Your doctor will regularly monitor your blood counts after you receive Kymriah as you may experience a reduction in the number of blood cells and other blood components .

Do not donate blood, organs, tissues or cells.

Children and adolescents

• There is limited experience with Kymriah in paediatric patients below the age of 3 years.
• Kymriah is not recommended to be used in children and adolescents below 18 years of age to treat DLBCL . This is because there is limited experience in the treatment of non -Hodgkin lymphoma in this age group.
• Kymriah should not be used in children and adolescents below 18 years of age to treat FL . This is because 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. This is because other medicines can affect the way Kymriah works.

In particular, you must not be given certain vaccines called live vaccine s:

• in the 6 weeks before you are given the short course of chemotherapy (called lymphodepleting chemotherapy) to prepare your body for the Kymriah cells.
• during Kymriah treatment.
• after treatment while the immune system is recovering.

Talk to your doctor if you need to have any vaccinations.

Before you are given Kymriah tell your doctor or nurse if you are taking any medicines that we aken your immune system such as corticosteroids, since these medicines may interfere with the effe ct of Kymriah.

46 Pregnancy and breast -feeding If you are pregnant or breast -feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine. This is because the effects of Kymriah in pregnant or breast -feeding women are not known, and it may harm your unborn baby or your newborn/infant .

• If you become pregnant or think you may be pregnant after treatment with Kymriah, talk to your doctor immediately.
• You will be given a pregnancy test before treatment starts. Kymriah should only be given if the result shows you are not pregnant .

Contraception for women and men Discuss pregnancy with your doctor if you have received Kymriah.

Driving and using machines

Some people may feel confused, have problems such as altered or decreased consciousness, confusion and seizures (fits) after being given Kymriah. Therefore, do not drive, use machines, or take part in activities that need you to be alert for in the 8 weeks following infusion.

Kymriah contains sodium, dimethyl sulfoxide (DMSO) , dextran 40 and potassium

This medicine contains 24.3 to 121.5 mg sodium (main component of cooking/table salt) in each dose.

This is equivalent to 1 to 6% of the recommended maximum daily dietary intake of sodium for an adult.

This medicine contains dextran 40 and DMSO (substances used to preserve frozen cells), both of which can sometimes cause difficulty breathing and/or dizziness (possible symptoms of serious allergic or hypersensitivity reactions) . You should be observed closely during the infusion period.

This medicin e contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially “potassium – free”.

💊 3. How Kymriah is given

Kymriah will always be given to you by a doctor in a qualified treatment centre .

Giving blood to make Kymriah Kymriah is made from your own white blood cells.

• Your doctor will take some of your blood using a catheter placed in your vein (a procedure called leukapheresis). Some of your white blood cells are separated from your blood and the rest of your blood is returned to your vein . This can take 3 to 6 hours and may need to be repeated.
• Your white blood cells are frozen and sent away to make Kymriah. It usually takes about 3 to 4 weeks to make Kymriah but the time may vary .
• Kymriah is a treatment that is manufactured specifically for you .
• Before you are given Kymriah, your doctor may give you a type of treatment called lymphodepleting chemotherapy for a few days to prepare your body.

Cancer treatment while Kymriah is being made During the period w hile Kymriah is being made, your lymphoma or leuk aemia may get worse and your doctor may decide to use an additional treatment (known as “bridging therapy”) to stabilise your cancer by stopping new cancer cells from developing . This treatment may lead to side effects and these may be severe or life -threatening. Your doctor will inform you of the potential side effects of this treatment.

Other medicine s given immediately before Kymriah treatment During the 30 to 60 minutes before you are given Kymriah you may be given other medicines. This is to help prevent infusion reactions and fever. These other medicines may include:

• Paracetamol
• An antihistamine such as diphenhydramine.

47 How Kymriah is given

• Your doctor will check that the individual patient identifiers on the Kymriah infusion bag match up to you.
• Your doctor will give you Kymriah by infusion, which means it will be given as a drip through a tube in your vein. This usually takes less than 1 hour. During the infusion your doctor will check if you have difficulty breathing or dizziness (possible symptoms of an allergic reaction).
• Kymriah is a one -time treatment.

After Kymriah is given

• Plan to stay within 2 hours ’ travel from the hospital where you were treated for at least 4 weeks after you have been given Kymriah. During the first week after treatment, y our doctor may recommend that you return 2 to 3 times , or more frequently , to the hospital . This is so your doctor can check if your treatment is working and help you if you have any side effects.

If you miss an appointment If you miss an appointment, call your doctor or the hospital as soon as possible to reschedule.

❗ 4. 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 the Kymriah infusion .

They usually happen in the first 8 weeks after the infusion, but can also develop later :

Very common: may affect more than 1 in 10 people

• high fever and chills. These may be symptoms of a serious condition called cytokine release syndrome which may be life -threatening or fatal . Other symptoms of cytokine release syndrome are difficulty breathing, nausea, vomiting, diarrhoea, loss of appetite, fatigue, muscle pain, joint pain, swelling, low blood pressure, fast heartbeat, headache, heart, lung and kidney failure and liver injury . These symptoms almost always occur within the first 14 days after treatment with Kymriah, but in some patients can also develop later .
• problems such as altered thinking or decreased consciousness, loss of contact with reality, confusion, agitation, seizures, difficulty speaking and understanding speech , difficulty walking .

These may be symptoms of a condition called immune effector cell -associated neurotoxicity syndrome (ICANS). These symptoms mostly occur within the first 8 weeks after treatment with Kymriah, but in some patients can also develop later.

• feeling warm, fever, chills or shivering , sore throat or mouth ulcers may be signs of an infection. Some infections may be life -threatening or fatal .

Common: may affect up to 1 in 10 people

• Rapid breakdown of tumour cells causing release of their contents into the bloodstream. This can interfere with the workings of various body organs , especially the kidneys, heart and nervous system (tumour lysis syndrome).

Other possible side effects Other side effects are listed below. If these side effects become severe or serious, tell your doctor immediately.

Very common (may affect more than 1 in 10 people)

• Pale skin, weakness, breathlessness due to low number of red blood cells or low haemoglobin
• Excessive or prolonged bleeding or bruising due to l ow number of platelets
• Fever with dangerously low white blood cell count
• Increased risk of infection due to abnormally low number of white blood cells
• Frequent and persistent infections due to decreased antibodies in your blood 48 • Weakness, abnormal heart rhythms, due to abnormal ly low level of blood salts including phosphorus , potassium
• High levels of liver enzymes or creatinine in the blood that show that your liver or kidneys are not working normally
• Raised blood pressure
• Shortness of breath, laboured breathing, rapid breathing
• Cough
• Abdominal pain, constipation
• Bone and back pain
• Skin rash
• Swollen ankles, limbs and face

Common (may affect up to 1 in 10 people)

• Fever, malaise, enlarged liver, yellow colo ur of your skin and eyes, low blood cell counts due to severe immune activation
• Dizziness or fainting, flushing, rash, itching, fever, shortness of breath or vomiting, abdominal pain, diarrhoea due to infusion -related reaction
• Rash, nausea, vomiting, diarrhoea including bloody stools (possible symptoms of graft -versus – host disease which is when transplanted cells attack your cells)
• Pain in the joints due to high level of uric acid
• Abnormal blood test results (high level of: phosph orus, potassium, calcium and sodium , fibrin d-dimer, serum ferritin; low level of: blood protein called albumin, sodium , magnesium )
• Convulsion, fits (seizures)
• Muscle spasms/cramping due to abnormally low level of blood salts including calcium
• Involuntary or uncontrollable movements
• Involuntary shaking of the body, difficulty writing, difficulty expressing thoughts verbally, impaired attention, sleepiness
• Tingling or numbness , difficulty moving because of nerve damage
• Decreased vision
• Thirst , low urine output, dark urine, dry flushed skin, irritability (possible symptoms of high level of sugar in blood )
• Weight loss
• Nerve pain
• Anxiety, irritability
• Severe state of confusion
• Difficulty sleeping
• Breathlessness, difficulty breathing when lying down, swelling of the feet or legs (possible symptoms of h eart failure ), fast or irregular heart beat, stopped heart beat
• Swelling and pain due to blood clots
• Swelling due to fluids leaking from blood vessels into the surrounding tissue
• Bloating and discomfort (abdominal distension) , due to an accumulation of fluid in the abdomen
• Dry mouth , sore mouth , bleeding in the mouth
• Yellow skin and eyes due to abnormal ly high levels of bilirubin in the blood
• Itching
• Excessive sweating, n ight sweats
• Flu-like illness
• Failure of multiple organs
• Fluid in the lungs
• Stuffy nose
• Defect in blood clotting (coagulopathy, increased international normali sed ratio, prolonged prothrombin time, decreased blood fibrinogen, prolonged activated partial thromboplastin time ) 49 Uncommon (may affect up to 1 in 100 people)
• Abnormal blood test results (high level of magnesium)
• Weakness or paralysis of limbs or face, difficulty speaking (possible symptoms of stroke as a result of reduced blood supply)
• Warm or rapid ly reddening skin
• Cough that produces phlegm or sometimes blood, fever, shortness of breath or difficulty breathing
• Difficulty in controlling movement

Rare (may affect up to 1 in 1 000 people)

• A new type of cancer beginning in a type of white blood cells called T -cells (secondary malignancy of T -cell origin)

Not known (frequency cannot be estimated from the available data)

• Difficulty breathing or dizziness (possible symptoms of an allergic reaction)
• Weakness or numbness in the arms or legs, worsening of or loss of vision, having fixed and irrational thoughts that are not shared by others, headache, impaired memory or thinking, unusual behaviour

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V.

By reporting side effects , you can help provide more information on the safety of this medicine.

🌡️ 5. How to store Kymriah

The following information is intended for doctors 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.

Store and transport ≤ -120°C. Do not thaw the product until it is ready to be used.

Do not use this medicine if the infusion bag is damaged or leaking.

📦 6. Contents of the pack and other information

What Kymriah contains

• The active substance is tisagenlecleucel . Each infusion bag of K ymriah contains tisagenlecleucel cell dispersion at a batch -dependent concentration of autologous T cells genetically modified to express an anti-CD19 chimeric antigen receptor (CAR -positive viable T cells). 1 or more bags contain a total of 1.2 × 106 – 6 × 108 CAR+ viable T cells.
• The other ingredients are glucose, sodium chloride, human albumin solution, dextran 40 for injection, dimethyl sulfoxide, sodium gluconate, sodium acetate, potassium chloride, magnesium chloride, sodium -N-acetyltryptophanate, sodium caprylate, aluminium, and water

for injections . See section 2, “Kymriah contains sodium, dimethyl sulfoxide (DMSO) , dextran 40 and potassium ”.

This medicine contains cells of human origin .

What Kymriah looks like and contents of the pack

Kymriah is a cell dispersion for infusion. It is supplied as an infusion bag containing a cloudy to clear, colourless to slightly 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 Sophie -Germain -Strasse 10 90443 Nuremberg Germany For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Novartis Pharma N.V.

Tél/Tel: +32 2 246 16 11 Lietuva SIA Novartis Baltics Lietuvos filialas Tel: +370 5 269 16 50 България Novartis Bulgaria EOOD Тел: +359 2 489 98 28 Luxembourg/Luxemburg Novartis Pharma N.V.

Tél/Tel: +32 2 246 16 11 Česká republika Novartis s.r.o.

Tel: +420 225 775 111 Magyarország Novartis Hungária Kft.

Tel.: +36 1 457 65 00 Danmark Novartis Healthcare A/S Tlf.: +45 39 16 84 00 Malta Novartis Pharma Services Inc.

Tel: +356 2122 2872 Deutschland Novartis Pharma GmbH Tel: +49 911 273 0 Nederland Novartis Pharma B.V.

Tel: +31 88 04 52 111 Eesti SIA Novartis Baltics Eesti filiaal Tel: +372 66 30 810 Norge Novartis Norge AS Tlf: +47 23 05 20 00 Ελλάδα Novartis (Hellas) A.E.B.E.

Τηλ: +30 210 281 17 12 Österreich Novartis Pharma GmbH Tel: +43 1 86 6570 España Novartis Farmacéutica, S.A.

Tel: +34 93 306 42 00 Polska Novartis Poland Sp. z o.o.

Tel.: +48 22 375 4888 France Novartis Pharma S.A.S.

Tél: +33 1 55 47 66 00 Portugal Novartis Farma – Produtos Farmacêuticos, S.A.

Tel: +351 21 000 8600 Hrvatska Novartis Hrvatska d.o.o.

Tel. +385 1 6274 220 România Novartis Pharma Services Romania SRL Tel: +40 21 31299 01 51 Ireland Novartis Ireland Limited Tel: +353 1 260 12 55 Slovenija Novartis Pharma Services Inc.

Tel: +386 1 300 75 50 Ísland Vistor hf.

Sími: +354 535 7000 Slovenská republika Novartis Slovakia s.r.o.

Tel: +421 2 5542 5439 Italia Novartis Farma S.p.A.

Tel: +39 02 96 54 1 Suomi/Finland Novartis Finland Oy Puh/Tel: +358 (0)10 6133 200 Κύπρος Novartis Pharma Services Inc.

Τηλ: +357 22 690 690 Sverige Novartis Sverige AB Tel: +46 8 732 32 00 Latvija SIA Novartis Baltics Tel: +371 67 887 070

This leaflet was last revised in

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu

🩺 Information intended for healthcare professionals only

Precautions to be taken before handling or administering the medicinal product 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.

Preparation prior to administration 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 t he 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.

Inspection and thawing of the infusion bag(s) 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 guidelines on handling of biological waste .

Administration 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), e nsure 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 Med icines Agency shortage catalogue, ensure that suitable alternative measures to treat cytokine release syndrome are available on site.

The p atient’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 .

53 Kymriah should be administered as an intravenous infusion using 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 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 Measures to take in case of accidental exposure 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.

Precautions to be taken for the disposal of the medicinal product Unused medicinal product and a ll 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 .

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Kymriah (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/18/1297).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.