Yescarta 0,4 - 2 x 10e8 celulas dispersion para perfusion

Label: information for the patient

Yescarta0.4 – 2x108cellsdispersion for infusion

axicabtagene ciloleucel(CAR T cells+viable)

This medication is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section4 includes information on how to report these adverse effects.

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• Your doctor will provide you with a patient information leaflet. Read it carefully and follow the instructions.
• Always show the patient information leaflet to your doctor or nurse who treats you or if you visit the hospital.
• If you have any questions, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this label. See section4.

Yescarta is a gene therapy medication used for the treatment of adult patients with aggressive diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) that affect the lymphatic tissue (part of the immune system), which in turn affects a type of white blood cells called B cells and other organs in the body. The excessive accumulation of these abnormal white blood cells in tissues is the cause of symptoms that may be present. It is used for the treatment of these diseases when other available medications are no longer effective for their treatment.

The medication is prepared specifically for you, as a single administration of your modified own white blood cells.

No use Yescarta:

• If you are allergic to axicabtagene ciloleucel or any of the other components of this medication (listed in section 6).
• If you cannot receive a treatment called lymphodepletion chemotherapy that reduces the number of white blood cells in your blood (also see section 3, How Yescarta is administered).

Warnings and precautions

Yescarta is prepared from your own white blood cells and should only be administered to you (autologous use).

Before Yescarta is administered, you must consult your doctor if:

• You have nervous system problems (such as seizures, stroke, or memory loss).
• You have kidney problems.
• You have a low number of blood cells (blood counts).
• You have had a hematopoietic stem cell transplant in the last 4 months.
• You have any lung, heart, or blood pressure problems (low or high).
• You have signs or symptoms of graft-versus-host disease. This occurs when the transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhea, and bloody stools.
• You notice that your cancer symptoms are getting worse. If you have lymphoma, they may include fever, feeling weak, night sweats, and sudden weight loss.
• You have an infection. It will be treated before Yescarta infusion is administered.
• You have had hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

If any of the above apply to you (or you are unsure), consult your doctor before Yescarta is administered.

Analysis and checks

Before Yescarta is administered, your doctor:

• Will examine your lungs and heart, and check your blood pressure.
• Will look for signs of infection; any infection will be treated before Yescarta is administered.
• Will check if your cancer is getting worse.
• Will look for signs of graft-versus-host disease that may occur after a transplant.
• Will check your uric acid and the number of cancer cells in your blood. This will show if you are likely to develop a complication called tumor lysis syndrome. You may be given medications to help prevent the complication.
• Will check if you have hepatitis B, hepatitis C, or HIV infection.
• Will check if you were vaccinated in the last 6 weeks or if you are planning to receive a vaccine in the next few months.

After Yescarta is administered

If you notice any of the following symptoms, inform your doctor or nurse immediately:

• Chills, extreme fatigue, weakness, dizziness, headache, cough, difficulty breathing, or rapid heart rate. These may be symptoms of a complication called cytokine release syndrome. Take your temperature twice a day for 3 to 4 weeks after Yescarta treatment. If your temperature is high, consult your doctor immediately.
• Seizures, tremors, or difficulty speaking or altered speech, loss of consciousness or reduced levels of consciousness, confusion, and disorientation, loss of balance or coordination.
• Fever, which may be a symptom of infection.
• Extreme fatigue, weakness, and difficulty breathing, which may be symptoms of low red blood cell levels.
• Bleeding or easy bruising, which may be symptoms of low platelet levels.
• Blurred vision, loss of vision, or double vision, difficulty speaking, weakness, or clumsiness of an arm or leg, a change in gait or balance, or personality changes, changes in thought, memory, and orientation that lead to confusion. All of these may be symptoms of a severe and potentially fatal brain disease called multifocal progressive leukoencephalopathy (MPL). These symptoms may start several months after treatment is completed and usually develop slowly and gradually over weeks or months. It is essential that your family members or caregivers are aware of these symptoms.

Your doctor will check your blood counts frequently, as the number of blood cells and other blood components may decrease.

Do not donate blood, organs, tissues, or cells for transplantation.

If you are in any of these circumstances (or are unsure), consult your doctor or nurse before Yescarta is administered.It may be necessary for your doctor to provide you with special medical care during Yescarta treatment.

In some cases, it may not be possible to administer Yescarta. For example:

• If the Yescarta infusion is delayed more than 2 weeks after you received preparatory chemotherapy, you may need to receive additional preparatory chemotherapy.

Children and adolescents

Yescarta should not be administered to children and adolescents under 18 years old.

Other medications and Yescarta

Inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication.

Before Yescarta is administered, inform your doctor or nurse if you are taking any medication that weakens your immune system, such as corticosteroids, as these medications may interfere with the effect of Yescarta.

You should not receive certain vaccines called live virus vaccines, particularly:

• During the 6 weeks before you receive the short cycle of chemotherapy (called lymphodepletion) to prepare your body for Yescarta cells.
• During Yescarta treatment.
• After treatment while your immune system is recovering.

Consult your doctor if you need any vaccine.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before this medication is administered.This is because the effects of Yescarta on pregnant women or breastfeeding women are unknown, and it may harm the fetus or infant.

• If you are pregnant or think you may be pregnant after Yescarta treatment, consult your doctor immediately.
• You will have a pregnancy test before treatment begins. Yescarta should only be administered if the results show you are not pregnant.

Discuss pregnancy with your doctor if you received Yescarta.

Driving and operating machinery

Some people may feel tired, dizzy, or experience tremors after Yescarta administration. If this happens to you, do not drive or operate heavy machinery for at least 8 weeks after infusion or until your doctor confirms you have fully recovered.

Yescarta contains sodium, dimethyl sulfoxide (DMSO), and residual gentamicin

This medication contains 300 mg of sodium (main component of table salt/for cooking) in each infusion bag. This is equivalent to 15% of the recommended daily maximum sodium intake for an adult.

This medication contains DMSO and residual gentamicin, which may cause severe allergic reactions.

Yescarta will always be administered by a healthcare professional.It is administered by infusion (perfusion) in a vein (intravenous route).

• Since Yescarta is prepared from your own white blood cells, your cells will be extracted to prepare your medication. Your doctor will extract a small amount of blood with a catheter placed in your vein (a procedure called leucaféresis). Some white blood cells are separated from the blood, and the rest of the blood is returned to the vein. This may take 3 to 6 hours and may need to be repeated.
• Your white blood cells are frozenand sent to prepare Yescarta. You will usually receive your Yescarta treatment in 3 to 4weeks, but the time may vary..

Other medications administered before Yescarta treatment

During the 30 to 60minutes before Yescarta is administered, you may be given other medications. This helps to prevent infusion reactions and fever. These other medications may include:

• Paracetamol.
• An antihistamine such as diphenhydramine.

Before receiving Yescarta, you will be given other medications, such as preparatory chemotherapy, so that the modified white blood cells in Yescarta can multiply in your body once the medication is administered.

Your doctor or nurse will carefully check that the medication to be administered belongs to you..

How Yescarta is administered

Yescarta will always be administered by a doctor in a qualified medical center.

• Yescarta is administered in a single dose.
• Your doctor or nurse will administer a single infusion of Yescarta through a catheter placed in a vein (intravenous infusion) for about 30minutes.

You should only receive the Yescarta infusion in a qualified medical center and be discharged when your doctor considers you to be in a condition to return home.

Your doctor mayperform blood tests to detect possible adverse effects.

After Yescarta administration

• Plan to stay in a place close to the hospital where you were treated for at least 4weeks after receiving Yescarta. Your doctor will recommend that you return to the hospital daily for at least 10days and will consider whether you need to be hospitalized for the first 10days after the infusion. This is to check if your treatment is working and to help you if you experience any adverse effects.

If you do not attend an appointment

Please contact your doctor or the qualified medical center as soon as possible toschedule another appointment.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

Yescarta can cause side effects related to the immune system or the nervous system. Yescarta may also increase the risk of infection. These side effects can be severe or potentially fatal, and may even cause death.

Inform your doctor immediately if you experience any of the following side effects after receiving Yescarta, as you may need urgent medical treatment:

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

• Fever, chills, low blood pressure that may cause symptoms such as dizziness or lightheadedness, rapid heartbeats, irregular heartbeats (arrhythmia), low oxygen levels in the blood that may cause shortness of breath or difficulty breathing. These may be signs of a serious disease called cytokine release syndrome.
• Loss of consciousness or decreased level of consciousness, confusion or disorganized thinking, memory loss, difficulty speaking or speaking in a slurred manner, difficulty understanding speech due to brain function alterations (encephalopathy). Other signs of involuntary tremors (tremor), sudden confusion with agitation, disorientation, hallucinations or irritability (delirium), lack of energy or strength, muscle weakness, difficulty moving (motor dysfunction).
• Sensation of heat, fever, chills, or shivering, which may be signs of infection (including bacterial or viral infection). Infections may be due to an abnormally low number of white blood cells or low levels of antibodies called "immunoglobulins" in the blood, which help fight infections.

Other severe side effects that require immediate medical assistance are:

Common (may affect up to 1 in 10 people)

• Seizures (crises, including prolonged and potentially fatal crises).
• Sudden and unexpected stoppage of the heart (cardiac arrest) or heart failure
• Blood clots: symptoms may include chest pain or upper back pain, difficulty breathing, coughing up blood or colicky pain, swelling in one leg, warm and darkened skin around the painful area
• Inability to breathe on your own (respiratory insufficiency)
• Renal insufficiency that causes your body to retain fluids
• Fluid accumulation in the lungs (pulmonary edema) that may cause difficulty breathing

Rare (may affect up to 1 in 100 people)

• Inflammation and swelling of the spinal cord that may cause partial or total paralysis of the limbs and trunk.

If you notice any of the above-mentioned side effects, inform your doctor immediately. Do not attempt to treat your symptoms with other medications without consulting your doctor.

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in Appendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

This information is intended solely for physicians.

Do not use this medication after the expiration date that appears on the label of the container and the infusion bag.

It must be stored frozen in the vapor phase of liquid nitrogen ≤ -150°C until the moment of thawing for use.

Do not re-freeze.

Yescarta Composition

• The active ingredient is axicabtagene ciloleucel. Each individual patient-specific infusion bag contains a dispersion of anti-CD19 CAR T cells in approximately 68 ml, for a target dose of 2 x 10^6 viable anti-CD19 CAR T cells/kg.

• The other components (excipients) are: Cryostor CS10 (contains DMSO), sodium chloride, human albumin. See section 2 “Yescarta contains sodium, dimethyl sulfoxide (DMSO) and residual gentamicin”

This medicine contains genetically modified human blood cells.

Appearance of the product and contents of the pack

Yescarta is a transparent to opaque, white to red cellular dispersion, supplied in an individually packaged infusion bag in a metallic container. A single infusion bag contains approximately 68 ml of cellular dispersion.

Marketing Authorization Holder and Responsible Person

Kite Pharma EU B.V.

Tufsteen 1

2132 NT Hoofddorp

Netherlands

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

Last update of this leaflet:

Other sources of information

Further information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. There are also links to other websites on rare diseases and treatments.

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This information is intended for healthcare professionals:

Please read all the information related to this procedure before administering Yescarta.

Precautions to be taken before handling or administering the medicinal product

In the administration centre, Yescarta should be transported in closed, breakage-proof and leak-proof containers.

Healthcare professionals handling Yescarta will take the necessary precautions (wear gloves and goggles) to avoid the possible transmission of infectious diseases.

The working surfaces and materials that have come into contact with Yescarta should be disinfected with an appropriate disinfectant.

Preparation before administration

• Verify that the patient's identification (ID) matches the patient identifiers on the Yescarta container.
• Do not remove the Yescarta infusion bag from the metallic container if the patient information on the specific patient label does not match the patient being treated.
• Once the patient ID has been confirmed, remove the Yescarta infusion bag from the metallic container.
• Verify that the patient information on the metallic container label matches the information on the infusion bag label.
• Inspect the product bag for integrity before thawing. If the bag is damaged, follow local guidelines for the treatment of human origin waste (or contact Kite immediately).

Thawing

• Place the infusion bag in a second bag.
• Thaw Yescarta to an approximate temperature of 37°C, warming it in a water bath or by dry thawing, until no ice is visible in the infusion bag. Gently mix the contents of the infusion bag to eliminate cell aggregates. If cell aggregates continue to be visible, continue to gently mix the contents of the infusion bag. Small cell aggregates should be removed by gentle manual mixing. Yescarta should not be washed, centrifuged, or resuspended in a new medium before infusion. Thawing takes approximately 3 to 5 minutes.
• Once thawed, Yescarta is stable at room temperature (20°C to 25°C) for up to 3 hours. However, infusion of Yescarta should be started within 30 minutes of complete thawing.

Administration

• DO NOT use a leucodepletion filter.
• The medicinal product should be administered in a qualified medical centre, by one or more experienced physicians in the treatment of malignant hematological neoplasms and who have received training on the administration and treatment of patients treated with Yescarta.
• Ensure that at least one dose of tocilizumab per patient and an emergency kit are available before infusion and during the recovery period. Hospitals should have access to an additional dose of tocilizumab within 8 hours of each previous dose. In the exceptional case where tocilizumab is not available due to a shortage listed in the European Medicines Agency's shortage catalogue, ensure that alternative measures are available in the centre to treat SLC in place of tocilizumab.
• Verify that the patient's identity matches the patient identifiers on the infusion bag.
• Yescarta is intended only for autologous use.
• Yescarta should be administered as an intravenous infusion using non-latex intravenous lines and without a leucodepletion filter over a period of 30 minutes, either by gravity or using a peristaltic pump.
• During the infusion of Yescarta, gently agitate the infusion bag to prevent cell aggregates. The entire contents of the infusion bag should be administered.
• Before infusion, use a sodium chloride 9 mg/ml (0.9%) solution (0.154 mmol of sodium per ml) to prime the lines, as well as to flush them after infusion.
• Once the total volume of Yescarta has been infused, the infusion bag should be flushed with between 10 and 30 ml of a sodium chloride 9 mg/ml (0.9%) solution for injection by reverse priming with the aim of ensuring the infusion of as many cells as possible to the patient.

Measures to be taken in case of accidental exposure

In case of accidental exposure, follow local guidelines for the treatment of human origin waste. The working surfaces and materials that have come into contact with Yescarta should be disinfected with an appropriate disinfectant.

Precautions to be taken for the disposal of the medicinal product

The unused medicinal product and all materials that have come into contact with Yescarta (solid and liquid waste) should be treated and disposed of as potentially infectious waste according to local guidelines for the treatment of human origin waste.