Yescarta

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse
• 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 or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Yescarta is and what it is used for
2. What you need to know before you are given Yescarta
3. How Yescarta is given
4. Possible side effects
5. How to store Yescarta
6. Contents of the pack and other information

The white blood cells are taken from your blood and are genetically modified so that they can target the cancer cells in your body. When Yescarta is infused into your blood, the modified white blood cells will kill the cancer cells.

• if you are allergic to axicabtagene ciloleucel or any of the other ingredients of this medicine (listed in section 6).
• if you cannot receive treatment, called lymphodepleting chemotherapy, which reduces the number of white blood cells in your blood (see also section 3, How Yescarta is given).

Yescarta is made from your own white blood cells and must only be given to you (autologous use). Patients treated with Yescarta 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 Yescarta and similar medicines. Talk to your doctor if you experience any new swelling of your glands (lymph nodes) or changes in your skin such as new rashes or lumps.

• have problems with your nervous system (such as fits, stroke, or memory loss).
• have kidney problems.
• have low blood cell levels (blood counts).
• have had a stem cell transplant in the last 4 months.
• have any lung, heart or blood pressure (low or raised) problems.
• 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.
• notice the symptoms of your cancer are getting worse. If you have lymphoma this might include fever, feeling weak, night sweats, sudden weight loss.
• have an infection. The infection will be treated before the Yescarta infusion.
• have had hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.

If any of the above apply to you (or you are not sure), talk to your doctor before being given Yescarta. Your doctor may need to take special care of you during your treatment with Yescarta.

Before you are given Yescarta your doctor will:

• Check your lungs, heart, kidney and blood pressure.
• Look for signs of infection or inflammation; and decide whether you need to be treated before you are given Yescarta.
• Check if your cancer is getting worse.
• Look for signs of graft-versus-host disease that can happen after a transplant. This happens when transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhoea and bloody stools.
• 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.
• Check if you had a vaccination in the previous 6 weeks or are planning to have one in the next few months.
• Check if you have previously received a treatment that attaches to the protein called CD19.

In some cases, it might not be possible to go ahead with the planned treatment with Yescarta. If Yescarta infusion is delayed for more than 2 weeks after you have received lymphodepleting chemotherapy you may have to receive more chemotherapy (see also section 3, How Yescarta is given).

Tell your doctor or nurse immediately or get emergency help right away if you have any of the following:

• Chills, extreme tiredness, weakness, dizziness, headache, cough, shortness of breath, or rapid heartbeat, which may be symptoms of a condition known as cytokine release syndrome. Take your temperature twice a day for 3 to 4 weeks after treatment with Yescarta. If your temperature is high, see your doctor immediately.
• Fits, shaking, or difficulty speaking or slurred 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 an infection.
• 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.
• Blurred vision, loss of vision or double vision, difficulty speaking, weakness or clumsiness of an arm or a leg, a change in the way you walk or problems with your balance, personality changes, changes in thinking, memory and orientation leading to confusion. These may all be symptoms of a serious and potentially fatal brain condition known as progressive multifocal leukoencephalopathy (PML). These symptoms may start several months after treatment has ended and they usually develop slowly and gradually over weeks or months. It is important that your relatives or caregivers are also aware of these symptoms, since they may notice symptoms that you are not aware of.

If any of the above apply to you (or you are not sure), talk to your doctor or nurse.

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

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

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

Yescarta must not be used in children and adolescents below 18 years of age because Yescarta has not been studied in this age group.

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

Before you are given Yescarta tell your doctor or nurse if you are taking any medicines that weaken your immune system such as corticosteroids, since these medicines may interfere with the effect of Yescarta.

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

• In the 6 weeks before you are given the short course of chemotherapy (called lymphodepleting chemotherapy) to prepare your body for the Yescarta cells.
• During Yescarta treatment.
• After treatment while the immune system is recovering.

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

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 Yescarta in pregnant or breast-feeding women are not known, and it may harm your unborn baby or your breast-fed child.

• If you are pregnant or think you may be pregnant after treatment with Yescarta, talk to your doctor immediately.
• You will be given a pregnancy test before treatment starts. Yescarta can only be given if the results show you are not pregnant.

Discuss pregnancy with your doctor if you have received Yescarta.

Some people may feel tired, dizzy or have some shaking after being given Yescarta. Therefore, do not drive or use heavy machines until at least 8 weeks after infusion or until your doctor tells you that you have completely recovered.

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

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

During the 30 to 60 minutes before you are given Yescarta 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.

Prior to receiving Yescarta, you will be given other medicines such as lymphodepleting chemotherapy, which will allow your modified white blood cells in Yescarta to multiply in your body when the medicine is given to you.

Your doctor or nurse will check carefully that this medicine is yours.

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

• Yescarta is given in a single dose.
• Your doctor or nurse will give you a single infusion of Yescarta through a catheter placed into your vein (intravenous infusion) over about 30 minutes.
• Yescarta is the genetically modified version of your white blood cells. Your healthcare professional handling the treatment will therefore take appropriate precautions (wearing gloves and glasses) to avoid potential transmission of infectious diseases and will follow local guidelines on handling of waste of human-derived material to clean up or dispose of any material that has been in contact with it.

You must receive Yescarta infusion in a qualified treatment centre and be discharged only when your doctor thinks it is safe for you to go home.

Your doctor may do blood tests to check for side effects.

• You must stay within proximity of a hospital as discussed with your doctor for at least 4 weeks after you have been given Yescarta. Your doctor will recommend that you return to the hospital daily for at least 7 days and will consider whether you need to stay at the hospital as an in-patient for the first 7 days after infusion. This is so your doctor can check if your treatment is working and help you if you have any side effects.

Call your doctor or the qualified treatment centre as soon as possible to make another appointment.

Yescarta can cause side effects to your immune system or your nervous system. Yescarta can also increase your risk of getting an infection. These side effects may be serious or life-threatening, and can lead to death.

Tell your doctor immediately if you get any of the following side effects after being given Yescarta, as you may need urgent medical treatment:

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

• Fever, chills, low blood pressure which may cause symptoms such as dizziness or lightheadedness, fast heartbeat, irregular heartbeat (arrythmia), low oxygen in blood which can lead to shortness of breath or difficulty breathing. These may be signs of a serious condition called cytokine release syndrome.
• Loss of consciousness or decreased level of consciousness, confusion or disorganised thinking, memory loss, difficulty speaking or slurred speech, difficulty understanding speech due to disturbances of brain function (encephalopathy). Other signs include involuntary shaking (tremor), sudden confusion with agitation, disorientation, hallucination or irritability (delirium), lack of energy or strength, muscular weakness, difficulty moving (motor dysfunction).
• Feeling warm, fever, chills or shivering which may be signs of infection (including bacterial or viral). Infections can be due to abnormally low number of white blood cells or low level of antibodies called ‘immunoglobulins’ in the blood which help fight infections.

Other serious side effects which require immediate medical care are:

Common (may affect up to 1 in 10 people)

• Fits (seizures, including seizures that may be prolonged and life-threatening).
• Sudden, unexpected stopping of the heart (cardiac arrest) or heart failure.
• Blood clots: symptoms can include pain in the chest or upper back, difficulty breathing, coughing up blood or cramping pain, swelling in a single leg, warm and darkened skin around the painful area.
• Inability to breathe on one one’s own (respiratory failure).
• Failure of the kidneys causing your body to hold onto fluid.
• Build-up of fluids in lungs (pulmonary oedema) which can lead to difficulty in breathing.

Uncommon (may affect up to 1 in 100 people)

• Condition of severe systemic inflammation which symptoms may include fever, rash, enlarged liver, spleen and lymph nodes.
• Improper functioning of at least 2 organs (eg, liver, lungs and kidneys) that requires medical treatment and/or procedures to restore normal organ function.

The following other side effects have been reported with Yescarta.

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

• Decrease in the number of red blood cells (cells that carry oxygen): symptoms can include extreme tiredness with a loss of energy.
• Low number of cells that help clot the blood (thrombocytopenia): symptoms can include excessive or prolonged bleeding or bruising.
• Low levels of sodium or phosphate seen in blood tests.
• High levels of uric acid or sugar (glucose) seen in blood tests.
• Decreased appetite.
• Difficulty sleeping.
• Headache.
• Dizziness.
• Fast heartbeat.
• Irregular heartbeat (arrhythmia).
• Low blood pressure.
• High blood pressure.
• Cough.
• Nausea, constipation, diarrhoea, abdominal pain, vomiting.
• Increase in liver enzymes seen in blood tests.
• Skin rash or skin problems.
• Muscle and joint pain, back pain.
• Build‑up of fluids in tissue (oedema) which can lead to swelling, weight gain, and decreased output of urine.
• Extreme tiredness.

Common (may affect up to 1 in 10 people)

• Fungal infection.
• Alteration of the blood ability to form clots (coagulopathy): symptoms can include excessive or prolonged bleeding or bruising.
• Hypersensitivity: symptoms such as rash, hives, itching, swelling and anaphylaxis.
• Low levels of albumin, potassium or calcium seen in blood tests.
• Dehydration.
• Weight loss.
• Anxiety.
• Mood disorders.
• Loss of control of body movements.
• Weakness or inability to move on one side of the body, making it hard to perform everyday activities like eating or dressing.
• Loss of movement in muscles of the face.
• Pain in the hands or feet.
• Muscle spasm.
• Changes in vision which makes it difficult to see things (visual impairment).
• Low oxygen in blood.
• Fluid around the lungs (pleural effusion).
• Shortness of breath, difficulty breathing.
• Nasal inflammation.
• Dry mouth, difficulty swallowing.
• High levels of bilirubin seen in blood tests.
• Infusion related reactions: symptoms such as dizziness or fainting, flushing, rash, itching, fever, shortness of breath or vomiting, abdominal pain and diarrhoea.
• Pain.

Uncommon (may affect up to 1 in 100 people)

• Paralysis of all four limbs.
• Swelling of spinal cord which may cause partial or total paralysis of limbs and torso.
• Difficulty understanding numbers.
• Weakness in the legs or arms.
• Breakdown of muscle tissue that leads to the release of muscle fibre into the blood.

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).

Tell your doctor immediately if you get any of the side effects listed above. Do not try to treat your symptoms with other medicines on your own.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

Do not use this medicine after the expiry date which is stated on the container label and infusion bag after ‘EXP’.

Store frozen in vapour phase of liquid nitrogen ≤ -150 °C until thawed for use.

Do not refreeze.

• The active substance is axicabtagene ciloleucel. Each patient-specific single infusion bag contains a dispersion of anti-CD19 CAR T cells in approximately 68 mL for a target dose of 2 × 10⁶ anti-CD19 CAR-positive viable T cells/kg.
• The other ingredients (excipients) are: Cryostor CS10 (contains DMSO), sodium chloride, human albumin. See section 2 “Yescarta contains sodium, dimethyl sulphoxide (DMSO), and residual gentamicin”.

This medicine contains genetically modified human blood cells.

Yescarta is a clear to opaque, white to red dispersion for infusion, supplied in an infusion bag individually packed in a metal cassette. A single infusion bag contains approximately 68 mL of cell dispersion.