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

Prospect: information for the patient

Tecartus 0.4 – 2 × 108cells for infusion

Autologous CD3+ T cells transduced anti-CD19 (viable CAR+ T cells)

This medicine 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 section 4 includes information on how to report these adverse effects.

Read this prospect thoroughly before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• Your doctor will give you a patient information leaflet. Read it thoroughly 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 doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

1. How Tecartus is administered
2. Possible adverse effects

1. Storage of Tecartus
2. Contents of the package and additional information

Tecartus is a gene therapy medication used for the treatment of mantle cell lymphoma in adults. It is used when other medications are no longer effective for its treatment (refractory or relapsed mantle cell lymphoma). This medication is prepared specifically for you from your own modified white blood cells, known as autologous CD3+ transduced anti-CD19 cells.

Mantle cell lymphoma is a cancer that affects a part of the immune system (the body's defenses). This cancer affects a type of white blood cell called B lymphocytes. In mantle cell lymphoma, B lymphocytes grow uncontrollably and accumulate in lymphoid tissue, bone marrow, or blood.

How Tecartus works

Your white blood cells are extracted from your blood and genetically modified so that they can target cancer cells in your body. When you are administered the Tecartus infusion into your blood, the modified white blood cells will destroy the cancer cells.

You will not be given Tecartus

• if you are allergic to any of the other components of this medication (listed in section 6). If you think you may be allergic, consult your doctor for advice.
• if you cannot receive the medication to reduce the number of white blood cells in your blood (lymphodepletion chemotherapy) (see also section 3, "How Tecartus is administered").

Warnings and precautions

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

Analysis and checks

Before Tecartus is administered to you, your doctor:

• will examine your lungs, heart, and kidneys and check your blood pressure.
• will look for signs of infection or inflammation and decide if you should receive treatment before Tecartus is administered.
• will check if your cancer is getting worse.
• will look for signs of graft-versus-host disease that can occur after a transplant. This happens when the transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhea, and bloody stools.

• will check your uric acid and white blood cell count 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 scheduled to receive a vaccine in the next few months.
• will check if you have previously received a treatment that binds to a protein called CD19.

In some cases, it may not be possible to administer the planned treatment with Tecartus. If the Tecartus infusion is delayed more than 2 weeks after you received lymphodepletion chemotherapy, you may need to receive more chemotherapy (see also section 3, "How Tecartus is administered").

After Tecartus is administered

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

• chills, extreme fatigue, weakness, dizziness, headache, cough, difficulty breathing, rapid or irregular heartbeat, severe nausea, vomiting, or diarrhea; these may be symptoms of a complication called cytokine release syndrome. Take your temperature twice a day for 3 to 4 weeks after treatment with Tecartus. If your temperature is high, consult your doctor immediately.

• seizures, tremors, or difficulty speaking or altered speech, loss of consciousness or decreased level of consciousness, confusion, and disorientation, loss of balance or coordination.

• fever (e.g., temperature above 38°C), 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.

If any of the above applies to you (or you are unsure), consult your doctor or nurse.

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

You will be asked to register for at least 15 years to understand better the long-term effects of Tecartus.

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

Children and adolescents

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

Other medications and Tecartus

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

Before Tecartus 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 Tecartus.

You should not be given certain vaccines called live virus vaccines, particularly:

• during the 6 weeks prior to receiving the short course of lymphodepletion chemotherapy to prepare your body for Tecartus cells.
• during treatment with Tecartus.

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

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

Discuss pregnancy with your doctor if you received Tecartus.

Driving and operating machinery

Tecartus may cause problems, such as altered level of consciousness or decreased level of consciousness, confusion, and seizures (convulsions), in the 8 weeks after administration.

Do not drive, do not use machines, or participate in activities that require close attention for at least 8 weeks after treatment with Tecartus or until your doctor confirms you have fully recovered.

Tecartus contains sodium, dimethyl sulfoxide (DMSO), and gentamicin

This medication contains 300 mg of sodium (main component of table salt/for cooking) in each infusion. This is equivalent to 15% of the recommended daily maximum sodium intake for an adult. It also contains DMSO and gentamicin, which may cause severe hypersensitivity reactions.

Tecartus will always be administered by a healthcare professional.

• Since Tecartus 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 a vein (a procedure calledleucaféresis). 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 will be sent to a manufacturing center to produce Tecartus. It usually takes 2 to 3 weeks to produce Tecartus, but the time may vary.

Medications administered before Tecartus treatment

A few days before receiving Tecartus, you will be administered lymphodepletion chemotherapy, which will allow the modified white blood cells in Tecartus to multiply in your body once you are administered the medication.

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

• Paracetamol.

• An antihistamine such as diphenhydramine.

How Tecartus is administered

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

• Tecartus is administered in a single dose.
• Your doctor or nurse will administer a single infusion of Tecartus through a catheter placed in a vein (intravenous infusion) over 30 minutes.
• Tecartus is the genetically modified version of your white blood cells. The healthcare professional handling the treatment will therefore take the necessary precautions (wear gloves and glasses) to avoid possible transmission of infectious diseases and will follow local guidelines for the treatment of human origin material waste for cleaning and disposal of any material that has been in contact with said treatment.

After Tecartus administration

• You must remain in a location close to the hospital where you were treated for at least 4 weeks after the Tecartus treatment. Your doctor will recommend that you return to the hospital daily for at least 10 days or stay hospitalized for the first 10 days after the Tecartus treatment. This is to allow your doctor to check if your treatment is working and to help you if you experience any side effects.

If you cannot attend an appointment, please contact your doctor or treatment center as soon as possible to reschedule the appointment.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Do not try to treat side effects yourself.

Tecartus may cause side effects that can be severe or potentially life-threatening.Seek urgent medical attentionif you experience any of the following side effects after theTecartus infusion.

Very common: may affect more than 1 in 10 people

• Fever, chills, decreased blood pressure that may cause symptoms such as dizziness, drowsiness, accumulation of fluid in the lungs that can be severe and life-threatening (all of which are symptoms of a complication calledcytokine release syndrome).

• Loss of consciousness or decreased level of consciousness, confusion or loss of memory due to brain function disorders, difficulty speaking or altered speech, involuntary tremors(shaking), seizures (seizures),confusion with agitation, disorientation, hallucinations or irritability(delirium).
• Fever, chills, which may be signs of infection.

Other possible side effects

The following are other side effects. Inform your doctor immediately if these side effects become severe or serious.

Very common: may affect more than 1 in 10 people

• Abnormally low white blood cell count, which may increase the risk of infection.
• Low platelet count(thrombocytopenia), alteration of blood clotting ability: symptoms may include excessive or prolonged bleeding or bruising.

• High blood pressure.
• Decreased red blood cell count (the cells that transport oxygen): symptoms may include extreme fatigue with lack of energy.
• Extreme fatigue.
• Accelerated or slowed heart rate.

• Decreased oxygen levels that reach body tissues: symptoms may include changes in skin color, confusion, and rapid breathing.
• Difficulty breathing, cough.
• Nausea, constipation, diarrhea, abdominal pain, vomiting, difficulty swallowing.
• Muscle pain, joint pain, bone pain, pain in the body extremities.

• Lack of energy or strength, muscle weakness, difficulty moving, muscle spasms.
• Headache.

• Kidney problems that cause fluid accumulation in your body, fluid accumulation in tissues(edema)that may cause weight gain, difficulty breathing, and decreased urine excretion.

• Elevated uric acid levels in blood tests.
• Low levels of sodium, phosphate, potassium, or calcium in blood tests.

• Decreased appetite, mouth pain.
• Difficulty sleeping, anxiety.

• Swelling in the extremities, fluid accumulation around the lungs(pleural effusion).
• Skin rash.

• Low levels of immunoglobulins in blood tests, which may lead to infections.
• Increased levels of liver enzymes in blood tests.
• Blood clots: symptoms may include chest pain or upper back pain, difficulty breathing, coughing up blood, or pain with cramping, swelling only in one leg, dark and warm skin around the painful area.

• Nerve pain.

Common: may affect up to 1 in 10 people

• Low albumin levels in blood tests.

• Excessive bleeding.
• Irregular heart rhythm(arrhythmia).

• Loss of control over body movements.
• Dry mouth, dehydration.
• Lack of breath(respiratory insufficiency).

• Difficulty breathing that prevents you from expressing yourself with complete sentences and coughing due to fluid accumulation in the lungs.
• Increased intracranial pressure.

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 thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

This information is intended solely for physicians.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date appearing on the container label and the infusion bag after CAD.

This medication must be stored frozen in the vapor phase of liquid nitrogen ≤ - 150 °C until the time ofthawing for use.

Do not re-freeze.

This medication contains genetically modified human blood cells. Local guidelines for the treatment of human origin material waste should be followed for unused medication or waste. This medication will be administered by qualified healthcare professionals, who will be responsible for the correct disposal of the product. This will help protect the environment.

Composition of Tecartus

The active principle is autologous CD3+ cells transduced anti-CD19. Each individual infusion bag specific to each patient 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, sodium chloride, human albumin. See section 2 “Tecartus contains sodium”.

Appearance of the product and contents of the pack

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

Marketing Authorization Holder

Kite Pharma EU B.V.

Tufsteen 1

2132 NT Hoofddorp

Netherlands

Responsible Person

Kite Pharma EU B.V.

Tufsteen 1

2132 NT Hoofddorp

Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Last update of this leaflet:

This medicinal product has been authorised under a conditional approval.

This type of approval means that more information is expected to be obtained from this medicinal product. The European Medicines Agency will review the new information from this medicinal product at least once a year and this leaflet will be updated as necessary.

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 orphan medicinal products.

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

This information is intended for healthcare professionals only:

It is important to read all the information related to this procedure before administering Tecartus.Precautions to be taken before handling or administering the medicinal product

• Tecartus contains genetically modified cells. Follow local guidelines for the treatment of human origin material regarding these medicinal products.

• At the administration centre, Tecartus must be transported in closed, break-resistant, and leak-proof containers.
• Tecartus is prepared from the patient's autologous blood obtained by leukaapheresis. The patient's leukaapheresis material and Tecartus may pose a risk of transmission of infectious viruses to healthcare professionals (HP) handling the product. Therefore, healthcare professionals handling the patient's leukaapheresis material or Tecartus must take necessary precautions (wear gloves and glasses) to avoid possible transmission of infectious diseases.

Preparation of the infusion

• Check that the patient's identification (ID) matches the patient identifiers on the metallic container of Tecartus.
• Do not remove the infusion bag from the metallic container if the patient's information on the specific patient label does not match the patient being treated.

• Once the patient's ID has been confirmed, remove the infusion bag from the metallic container.

• Check that the patient's information on the metallic container label matches the information on the infusion bag label.
• Inspect the infusion bag to check the integrity of the packaging before thawing. If the infusion bag is damaged, follow local guidelines for the treatment of human origin material waste (or contact Kite immediately).

• Insert the infusion bag into a second bag.
• Thaw Tecartus 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. Mix the contents of the infusion bag gently to eliminate cell aggregates. If cell aggregates continue to be visible, mix the contents of the infusion bag gently. Small cell aggregates should be eliminated by gentle manual mixing. Tecartus should not be washed, centrifuged, or resuspended in a new medium before infusion. Thawing will take approximately 3 to 5 minutes.

• Once thawed, Tecartus is stable at room temperature (20 °C-25 °C) for up to 3 hours. However, infusion should be started within 30 minutes of complete thawing.

Do not use a leucodepletion filter.

Administration

• This medicinal product should be administered in a qualified medical centre by one or more doctors with experience in the treatment of malignant haematological diseases and who have received training on the administration and treatment of patients treated with Tecartus.

• Ensure that at least one dose of tocilizumab per patient and an emergency kit are available before infusion and during the recovery period. Hospitals and associated centres should have access to an additional dose of tocilizumab within 8 hours of each previous dose.

• Check that the patient's identity matches the patient identifiers on the infusion bag.
• Tecartus is intended only for autologous use.

• Tecartus 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 infusion, gently agitate the infusion bag to prevent cell aggregation. Administer the entire contents of the infusion bag.
• Before infusion, use a sterile 0.9% sodium chloride solution for injection to prime the lines, as well as to flush them after infusion. Once the total volume of Tecartus has been infused, flush the infusion bag with between 10 and 30 ml of a 0.9% sodium chloride solution for injection using reverse priming with the aim of ensuring the infusion of as many cells as possible to the patient.

Elimination of Tecartus

• All unused medicinal products or waste that have been in contact with Tecartus (solid and liquid waste) should be treated and disposed of in accordance with local guidelines for the treatment of human origin material waste. Surfaces and materials that may have come into contact with Tecartus should be decontaminated with an appropriate disinfectant.

Accidental exposure

• Accidental exposure to Tecartus should be avoided. In the event of accidental exposure, follow local guidelines for the treatment of human origin material, which may include washing contaminated skin and removing contaminated clothing.