Aucatzyl 410 x 10^6 Cell Dispersion for infusion

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

Aucatzyl, also known as obecabtagene autoleucel, is a type of medicine called a ‘CAR-T cell-based gene therapy’. The medicine is made especially for you from your own white blood cells, called T cells.

Aucatzyl is used to treat adult patients with B cell acute lymphoblastic leukaemia, a type of blood cancer that affects white blood cells in your bone marrow called B lymphoblasts. It is given when previous treatment for your cancer has not worked, or the cancer has come back.

Aucatzyl is made by taking T cells from your blood and putting a new gene into them. This enables T cells to target the cancer cells in your body.

When Aucatzyl is infused into your blood, the modified T cells will kill the cancer cells.

Aucatzyl will be given to you by 2 infusions that are separated by about 9 days to achieve the total target dose. The amount of Aucatzyl given in the first infusion and second infusion will depend on the extent of your leukaemia. The total target dose of Aucatzyl is not affected by the extent of your leukaemia.

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

• 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 is used to reduce the number of white blood cells in your blood (see also section 3, how Aucatzyl is given).

Talk to your doctor or nurse before you are given Aucatzyl.

Aucatzyl is made from your own white blood cells and must only be given to you (autologous use).

Patients treated with Aucatzyl 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 other 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.

Before you are given Aucatzyl your doctor will:

• Check if you have any lung, heart, liver or kidney problems, especially if you are being treated with oxygen.
• Check if you have had chemotherapy before and had serious side effects that are not resolved.
• Look for signs of infection and decide whether you need to be treated before you receive Aucatzyl.
• Check for signs of active graft versus host disease if you have previously had a stem cell transplantation. Your doctor will not take your blood cells to make Aucatzyl until 3 months after you had your stem cell transplantation. This is to reduce the risk of worsening graft versus host disease.
• Check if you have or had diseases affecting the central nervous system. This includes conditions such as epilepsy, stroke, severe brain injuries or mental illnesses in the last 3 months.
• Check if your cancer is getting worse. Symptoms of your cancer getting worse might include fever, feeling weak, bleeding gums and bruising.
• Check if your cancer has spread to the brain.
• 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 are pregnant, if you think you may be pregnant, or if you plan to become pregnant (see sections “Pregnancy and breast-feeding” and “Contraception for women and men” below).

Tell your doctor before you are given Aucatzyl if any of the above apply to you, or you are not sure.

After you have been given Aucatzyl

• Look out for serious side effects. You must tell your doctor or nurse straight away because you may need treatment for them. See section 4 under ‘Serious side effects’.
• You will be monitored daily for 14 days after the first infusion. Your doctor will decide how often you will be monitored after the first 14 days and will continue monitoring for a least 4 weeks after infusion.
• Your doctor will regularly check your blood counts as the number of blood cells may decrease or if already low the number of blood cells may remain low.
• Stay close to the treatment centre where Aucatzyl was administered for at least 4 weeks. See section 3.
• The second infusion of Aucatzyl to achieve the complete total target dose will be given to you about 9 days after the first dose.
• If you experience a serious side effect/s after the first infusion, your second dose of Aucatzyl may be delayed or discontinued.

You will be asked to enrol in a long-term follow-up scheme to better understand the long-term effects of Aucatzyl.

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

There is not any experience of use of Aucatzyl in children and adolescents below 18 years of age.

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

In particular, tell your doctor or nurse before you are given Aucatzyl if:

• you are taking any medicines that weaken your immune system such as corticosteroids, since these medicines may interfere with the effect of Aucatzyl;
• you are taking any herbal remedies.

See section 3 for information about the medicines you will be given before receiving Aucatzyl.

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 Aucatzyl.
• During Aucatzyl 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 receiving this medicine. This is because the effects of Aucatzyl in pregnant or breast-feeding women are not known, and it may harm your unborn baby or your breast-fed child.

You will be given a pregnancy test before treatment starts. Aucatzyl should only be given if the result shows you are not pregnant.

Discuss pregnancy with your doctor if you have received Aucatzyl.

Do not drive, use tools or machines, or take part in activities that need you to be alert for at least 8 weeks following infusion. Aucatzyl can cause problems such as altered or decreased consciousness, confusion and fits (seizures). Consult with your healthcare professional over when you may resume driving or using tools and machines.

This medicine contains 1131 mg sodium (main component of cooking/table salt) in the total dose. This is equivalent to 57% of the recommended maximum daily dietary intake of sodium for an adult.

This medicine contains 39 mg potassium per dose. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

Aucatzyl also contains dimethyl sulfoxide which can cause severe allergic reactions.

Aucatzyl is made from your own white blood cells.

• Your doctor will take some of your blood using a tube (catheter) placed in your vein.
• Some of your white blood cells will be separated from your blood and the rest of your blood is returned to your body. This is called ‘leukapheresis’ and can take between 3 to 6 hours.
• Your white blood cells are sent away to manufacture Aucatzyl specifically for you.

• Your doctor may give you an additional treatment (known as “bridging therapy”) to stabilise your cancer, while you are waiting to receive Aucatzyl.
• A few days before you receive Aucatzyl, you will be given a type of treatment called lymphodepleting chemotherapy. This will allow the modified T cells in Aucatzyl to multiply in your body after Aucatzyl is given to you.
• Approximately 30 minutes before you are given Aucatzyl you will be given paracetamol. This is to help prevent infusion reactions and fever.

Aucatzyl will be given to you by a doctor in a qualified treatment centre experienced with this medicine.

• Your doctor will check that the Aucatzyl was prepared from your own blood by checking the patient identification information on the Aucatzyl infusion bag matches your details.
• Aucatzyl will be given to you in 2 infusions that are separated by approximately 9 days to achieve the complete total target dose.
• Aucatzyl is given by infusion (drip) through a tube into a vein.

• Stay close to the treatment centre for at least 4 weeks.
• You will be monitored daily for 14 days after the first infusion so that your doctor can check that the treatment is working and if needed help you with any side effects.
• Your doctor will assess if your second dose of Aucatzyl will proceed as planned. If you are experiencing any serious symptoms the second dose may need to be delayed or discontinued.

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

Aucatzyl may cause side effects that can be serious or life-threatening. Tell your doctor immediately if you get any of the following side effects after your Aucatzyl infusion:

• Fever and chills, low blood pressure, low oxygen in the blood which may cause symptoms such as fast or uneven heartbeat and shortness of breath. These may be signs of a serious problem called Cytokine Release Syndrome. Other symptoms of cytokine release syndrome are nausea, vomiting, diarrhoea, fatigue, muscle pain, joint pain, swelling, headache, heart, lung and kidney failure and liver injury.
• Confusion, shaking (tremor), difficulty speaking and understanding speech. These may be signs of serious problems with your nervous system called Immune effector Cell-associated Neurotoxicity Syndrome.
• Feeling warm, fever, chills, or shivering. These may be signs of infection which can be caused by low levels of blood cells called neutrophils.
• Feeling very tired, weak, and short of breath. These may be signs of low red blood cell levels (anaemia).
• Abnormally low number of white blood cells (neutropenia), which may increase your risk of infection.
• Bleeding or bruising more easily. These may be signs of low levels of blood cells known as platelets (thrombocytopenia).

If you get any of the side effects above after being given Aucatzyl, seek urgent medical help.

Other side effects are listed below. If these side effects become severe or serious, or if you are concerned about them, tell your doctor immediately.

Very common: may affect more than 1 in 10 people

• Nausea, constipation, diarrhoea, abdominal pain, vomiting
• Headache
• Abnormal brain function
• Dizziness
• Fever
• Fast heart rate
• Low blood pressure
• Pain, fatigue or tiredness, swelling, feeling weak
• Cough
• Decreased level of appetite
• Joint pain
• Rash
• Weight loss
• Abnormal blood test results
• Alteration of the blood’s ability to form clots (coagulopathy): symptoms can include excessive or prolonged bleeding or bruising
• Increase in liver enzymes seen in blood tests
• Fungal infection

Common: may affect up to 1 in 10 people

• Chills
• Haemophagocytic lymphohistiocytosis - white blood cells accumulate and damage organs, including the bone marrow, liver, and spleen, and destroy other blood cells
• Low antibody count (hypogammaglobulinaemia). It can put you at risk of infections and other diseases
• Sore throat or mouth ulcers, skin ulcers (may be signs of an infection)
• Irregular heartbeat
• Heart failure
• Acute loss of blood from a damaged blood vessel (haemorrhage)
• Infusion-related reaction
• Uncontrolled trembling or shaking movements in one or more parts of your body
• Delirium

In addition: a new type of cancer beginning in a type of white blood cells called T cells (secondary malignancy of T cell origin) has been reported for other similar medicines.

Tell your doctor if you have any of the side effects listed above. If these side effects become severe or serious, or if you are concerned about them, tell your doctor immediately.

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.

The active substance is obecabtagene autoleucel. The finished product is packaged in three or more infusion bags containing a target total of 410 × 10⁶ CD19 CAR-positive viable T cells to enable a split dosing regimen.

The other ingredients are: disodium edetate; dimethyl sulfoxide; human albumin solution; phosphate buffered saline: potassium chloride, potassium dihydrogen phosphate, sodium chloride, disodium phosphate, water for injections.

This medicine contains genetically modified human blood cells.

Aucatzyl is a colourless to pale yellow, very opalescent cell dispersion for infusion. It is supplied in three or more infusion bags individually packed within an overwrap in a metal cassette.

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