InfoCons Consumer Protection informs you – Aucatzyl – Package Leaflet

Before anything else

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• Your doctor will give you a Patient Card. Read it carefully and follow the instructions on it.
• Always show the Patient Card to the docto r or nurse when you see them or if you go to hospital.
• If you experience any side effects, immediately talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
• If you have any further questions, ask your doctor or nurse.

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

Aucatzyl is a gene therapy product that contains the active substance obecabtagene autoleucel. The medicine is made especially for you from your own T cells. T cells are a type of white blood cells that are important for your immune system (the body’s defences) to work properly.

Aucatzyl is a cancer medicine used in adults aged 26 years and above to treat B cell acute lymphoblastic leukaemia (B ALL), a type of blood cancer that affects white blood cells in your bone marrow called B lymphoblasts. It is used when your cancer has come back (relapsed) or has not improv ed with previous treatment (refractory).

The active substance in Aucatzyl, obecabtagene autoleucel, contains a patient’s own T cells, which have been genetically modified in a laboratory so that they make a protein called chimeric antigen receptor (CAR). CAR can attach to another protein on the surface of cancer cells called CD19. When a patient is given an infusion (drip) with Aucatzyl, the modified T cells attach to and kill the cancer cells, thereby helping to clear the cancer from the body.

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

⚠️ 2. What you need to know before you are given Aucatzyl

You must not be given Aucatzyl

• 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 advi ce.

47 • 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).

Warnings and precautions

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 cancers. There have been reports of patients developing T cell cancers after treatment with 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.

Tests and checks Before you are given Aucatzyl Your doctor will perform checks to decide how Aucatzyl should be given to you or if you need additional m edicines (see also section 3, How Aucatzyl is given). Based on the outcomes of the tests, your doctor might delay or change your planned treatments with Aucatzyl.

Your doctor will do the following tests and checks:

• Check if you have any lung, heart, liver or kidney problems.
• Look for signs of infection; any infection will be treated before you are given Aucatzyl.
• Check for signs and symptoms of graft versus host disease (GvHD) if you have had a stem cell transplantation (a procedure where a patient’s bone marrow is replaced to form new bone marrow) within the past 3 months. GvHD happens when transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhoea and bloody stools.
• 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 the 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.

You may have to receive treatment for any of these infections before you can be given Aucatzyl.

• Check if you have had a vaccination in the previous 6 weeks or are planning to have one in the next few months.

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

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

• Fever and chills, low blood pressure and 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 (CRS).

See section 4 for other symptoms of CRS.

• Loss of consciousness or decreased level of consciousness, involuntary shaking (tremor), seizures, difficulty speaking, slurred speech and understanding speech. These may be signs of serious problems with your nervous system called immune effector cell- associated neurotoxicity syndrome (ICANS).

48 • Feeling warm, fever, chills or shivering, sore throat or mouth ulcers. These may be signs of an infection which can be caused by low levels of white blood cells called neutrophils.

• Feeling very tired, weak, and short of breath. These may be signs of low red blood cell levels (anaemia).
• Bleeding or bruising more easily. These may be signs of low levels of blood platelets, components that help the blood clot (thrombocytopenia).

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

To minimise the above risks, you will be monitored for side effects daily for 14 days after the first infusion. Your doctor will deci de how often you will be monitored after the first 14 days and will continue monitoring for a least 4 weeks after. Your doctor may need to administer additional medicines to control the side effects, e.g., glucocorticosteroids, tocilizumab and/or antibioti cs.

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 (within 2 hours of travel) to the treatment centre where Aucatzyl was administered for at least 4 weeks. See section 3.

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

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

Children and adolescents

Aucatzyl should not be used in children and adolescents below 18 years of age.

Other medicines and Aucatzyl

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 befo re 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 have previously received a treatment that targets the CD19 protein.

Vaccinations 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.

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 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.

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

Driving and using tools and machines 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). See section 4, Possible side effects.

Aucatzyl contains sodium, potassium, and dimethyl sulfoxide (DMSO)

This medicine contains 1 131 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 al so contains DMSO which can cause severe allergic reactions.

💊 3. How Aucatzyl is given

Giving your own blood cells to make Aucatzyl 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 used to make Aucatzyl specially for you. This may take around 21 days.

Other medicines you will be given before Aucatzyl

• From day 6 to day 3 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. A delay in Aucatzyl treatment is possible depending on how you react to the chemotherapy.
• A bone marrow assessment is required before starting the lymphodepleting chemotherapy to determine the amount of Aucatzyl to be given in the first and second infusion.
• Approximately 30 minutes before you are given Aucatzyl you will be given paracetamol and diphenhydram ine (an anti -allergic). This is to help prevent infusion reactions and fever.

How Aucatzyl is given 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 is given by infusion (drip) into a vein.
• Aucatzyl will be given to you by 2 infusions that are separated by approxim ately 9 days to achieve the total target dose. The first infusion will last no more than 10 minutes. If you notice any side effects, please inform your doctor immediately. The second infusion will usually last less than one hour.

50 • The amount of Aucatzyl given in the first and second infusion will depend on the extent of your leukaemia. The dose of obecabtagene autoleucel given in the first and second infusions is adjusted based on your leukaemia’s severity. However, the total target dose remains unchanged no matter how advanced your leukaemia is .

Ask your doctor or nurse if you have doubts about how Aucatzyl is given to you.

After the first dose of Aucatzyl is given

• Stay close to the treatment centre (within 2 hours of travel) 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, such as CRS, ICANS or infections (see section 2, Warnings and precautions).
• 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 treatment m ay need to be stopped. After the second dose you also have to be monitored daily for 14 days after the infusion for possible side effects as in the first infusion.

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

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

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:

Very common: may affect more than 1 in 10 people

• 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 (CRS). 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.
• Loss of consciousness or decreased level of consciousness, involuntary shaking (tremor), seizures, difficulty speaking, slurred speech and understanding speech. These may be signs of serious problems with your nervous system called immune effector cell- associated neurotoxicity syndrome (ICANS).
• Feeling warm, fever, chills or shivering, mouth ulcers or sore throat. These may be signs of infection.
• Feeling very tired, weak, and shortness of breath. These may be signs of low levels of red blood cells (anaemia).
• Abnormally low levels of neutrophils, a type of white blood cell (neutropenia), which may increase your risk of infection.
• Bleeding or bruising more easily. These may be signs of low levels of platelets, components that help the blood to clot (thrombocytopenia).

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

Other possible side effects 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 commo n: may affect more than 1 in 10 people

• low number of white blood cells (leukopenia)
• low levels of lymphocytes, a type of white blood cell (lymphopenia)
• neutropenia with fever (febrile neutropenia)
• feeling sick (nausea)
• constipation
• diarrhoea
• belly (abdominal) pain
• vomiting
• headache
• abnormal brain function (encephalopathy)
• dizziness
• fever (pyrexia)
• rapid heartbeat (tachycardia)
• low blood pressure (hypotension)
• bleeding (haemorrhage)
• pain
• tiredness (fatigue)
• swelling (oedema)
• cough
• decreased appetite
• joint pain (musculoskeletal pain)
• rash
• fungal infection
• weight loss
• problems with blood clotting (coagulopathy)
• high levels of serum ferritin, a protein that stores iron in the body (hyperferritinaemia)
• increase in liver enzymes seen in blood tests

Common: may affect up to 1 in 10 people

• chills
• build-up of white blood cells, damaging organs, including the bone marrow, liver, and spleen, and destroying other blood cells (haemophagocytic lymphohistiocytosis)
• low levels of immunoglobulins (antibodies) in the blood leading to a high risk of infection (hypogammaglobulinaemia)
• inflammation of the lining of the mouth (stomatitis)
• irregular heartbeat (arrhythmia)
• heart (cardiac) failure
• infusion -related reaction including symptoms like fever, chills, rash, or difficulty breathing
• uncontrolled trembling or shaking movements in one or more parts of your body (tremor)
• confusion (delirium) Development of new types of cancer beginning in T cells (secondary malignancy of T cell origin) has been repo rted in patients using other CAR T 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.

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 Aucatzyl

The following information is intended for doctors only.

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

Store and transport frozen in the vapour phase of liquid nitrogen ≤ −150 °C. Do not thaw the product until it is ready to be used. Shelf life after thawing: 1 hour.

Do not refreeze.

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

Local guidelines on handling of waste of human -derived material should be followed for unused medicine or waste material.

📦 6. Contents of the pack and other information

What Aucatzyl contains

The active substance is obecabtagene autoleucel. The medicine is packaged in 3 or more infusion bags containing a target total of 410 × 10 6 anti-CD19 CAR -positive viable T cells to enable a split dosing regimen.

The other ingredients are disodium edetate, dimethyl sulfoxide (DMS O), human albumin solution and phosphate buffered saline (PBS), consisting of potassium dihydrogen phosphate, sodium chloride, disodium phosphate, potassium chloride, and water for injections. See section 2, Aucatzyl contains sodium, potassium and dimethyl sulfoxide (DMSO).

This medicine contains genetically modified human blood cells.

What Aucatzyl looks like and contents of the pack

Aucatzyl is a colourless to pale yellow, very opalescent dispersion for infusion. It is supplied in 3 or more infusion ba gs individually packed within an overwrap in a metal cassette. The metal cassettes are packed into a ModPak, which is transported in a cryoshipper.

Marketing Authorisation Holder

Autolus GmbH Im Schwarzenbach 4 79576 Weil am Rhein Germany Tel: 00800 0825 0829 (toll free, this number is valid in all EU countries)

Manufacturer

Marken Germany GmbH Moenchhofallee 13 65451 Kelsterbach Germany

This leaflet was last revised in

This medicine has been given ‘conditional approval’.

This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

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

This leaflet is available in all EU/EEA languages on the European Medicines Agency website. ————————————————————————————————————————-

🩺 Information intended for healthcare professionals only

Aucatzyl is intended for autologou s use.

Treatment consists of a split dose for infusion containing a dispersion of CD19 CAR- positive viable T cells in 3 or more infusion bags. The target dose of Aucatzyl is 410 × 10 6 CD19 CAR -positive viable T cells supplied in 3 or more infusion bags.

The treatment regimen consists of a split dose for infusion is to be administered on day 1 and day 10 (± 2 days):

• The dose regimen will be determined by the tumour burden assessed by bone marrow (BM) blast percentage from a sample obtained within 7 da ys prior to the start of lymphodepletion (see section below – ‘Bone marrow assessment’).
• Additionally, see the Release for Infusion Certificate (RfIC) and the Dose Schedule Planner for the actual cell counts and volumes to be infused and to select the appr opriate dose regimen.

Confirm availability of Aucatzyl before starting the lymphodepleting chemotherapy regimen (see SmPC section 4.4). The manufacturing time (time from leukapheresis receipt to product certification) is around 20 (range: 17-43) days.

Patients should be clinic ally re -assessed prior to administration of lymphodepleting chemotherapy and Aucatzyl to ensure the patient is eligible for therapy.

Receipt and storage of Aucatzyl:

• Aucatzyl is supplied directly to the cellular therapy laboratory associated with the inf usion centre in the vapour phase of a liquid nitrogen cryoshipper (≤ -150 °C).
• The patient’s identity must match the patient identifiers on the Aucatzyl RfIC and infusion bag label.
• Confirm the patient’s identity on the infusion bags with the patient iden tifiers on the cryoshipper , see Figure 1. Contact Autolus at 00800 0825 0829 if there are any discrepancies between the labels and the patient identifiers.
• Keeping the infusion bag(s) in the metal cassette(s), transfer Aucatzyl to the on -site controlled- access vapour phase of liquid nitrogen for storage ≤ -150 °C (until ready for thaw and administration).
• Time out of the vapour phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (it is recommended not to e xceed 90 seconds).

Administration Strictly follow Administration instructions to minimise dosing errors.

Aucatzyl is for autologous use only. The patient’s identity must match the patient identifiers on the Aucatzyl infusion bag. Do not infuse Aucatz yl if the information on the patient -specific label does not match the intended patient.

Preparation of the patient for Aucatzyl infusion Bone marrow assessment A BM assessment must be available from a biopsy and/or aspirate sample obtained within 7 days prior to the commencement of the lymphodepleting chemotherapy. The BM assessment w ill be used to determine the Aucatzyl dose regimen: High tumour burden regimen if blast percentage is > 20% or Low Tumour Burden Regimen if blast percentage is ≤ 20%, see Figure 2.

If BM assessment results are inconclusive:

• Repeat biopsy or aspirate (but only once). NOTE a repeat biopsy or aspirate must only be taken prior to lymphodepleting chemotherapy.
• If results remain inconclusive, proceed with High tumour burden regimen (i.e., administration of the 10 × 10 6 dose on day 1) per the Aucatzyl tumour burden adjusted split dose regimen.

Figure 2: Tumour burden adjusted split dose regimen 56 High Tumour Burden Dose Regimen (Bone marrow blast > 20% or inconclusive) Day 1 Day 10 (± 2 days) 10 × 106 dose administered via syringe* 100 × 106 dose administered via bag infusion+ and 300 × 106 dose administered via bag infusion+ Low Tumour Burden Dose Regimen (Bone marrow blast ≤ 20%) Day 1 Day 10 (± 2 days) 100 × 106 dose administered via bag infusion+ 10 × 106 dose administered via syringe* and 300 × 106 dose administered via bag infusion+

• Refer to RfIC for exact volume to be administered via syringe. The 10 × 106 CD19 CAR-positive

viable T cell bag configuration typically contains an overfill, and there it is important to withdraw Only the volume specified. + The 100 × 106 and 300 × 106 doses will be suspended in one or more infusion bags.

Bridging therapy Bridging therapy can be considered according to the prescriber’s choice prior to infusion to reduce tumour burden or stabilise the disease.

Pretreatment (lymphodepleting chemotherapy)

• Confirm availability of Aucatzyl prior to starting lymphodepleting chemotherapy. The manufacturing time (time from leukapheresis receipt to product certification) is around 20 days (range: 17- 43 days).
• Administer the lymphodepleting chemotherapy regimen before infusion of Aucatzyl: fludarabine (FLU) 30 mg/m2/day intravenously and cyclophosphamide (CY) 500 mg/m2/day intravenously. FLU and CY will be given together for 2 days and fludarabine alone on the third and fourth day (total dose: FLU 120 mg/m2; CY 1 000 mg/m2). For dose modifications of cyclophosphamide and fludarabine, see corresponding Summaries of Produ ct Characteristics of cyclophosphamide and fludarabine .
• Retreatment with lymphodepleting chemotherapy in patients who could not receive the Aucatzyl dose on day 1 as planned could be considered if there is an Aucatzyl dose delay of more than 10 days. Lymp hodepleting chemotherapy should not be repeated after the first dose of Aucatzyl is administered. Infuse Aucatzyl 3 days (± 1 day) after completion of lymphodepleting chemotherapy ( day 1), allowing a minimum 48-hour washout.

The Aucatzyl treatment should be delayed in some patient groups at risk. Retreatment with l ymphodepleting chemotherapy in patients who could not receive the Aucatzyl dose on day 1 as planned could be considered if there is an Aucatzyl dose delay of more than 10 days. A delay to the second split dose may be required to manage toxicities.

Premedication

• To minimise the risk of an infusion reaction, premedicate with paracetamol (1 000 mg orally) and diphenhydramine 12.5 to 25 mg intravenously or orally (or equivalent medicinal products) before the infusion of Aucatzyl . Prophylactic use of systemic corticosteroids is not recommended.

57 Preparation of Aucatzyl Before administration, it must be confirmed that the patient’s ide ntity matches the unique patient information on the Aucatzyl infusion bag and the RfIC presented in the Autolus Scheduling Portal, the RfIC will also be provided in the cryoshipper. The total number of Aucatzyl infusion bags to be administered must also be confirmed with the patient- specific information on the RfIC.

Precautions to be taken before handling or administering the medicinal product Aucatzyl must be transported within the facility in closed, break- proof, leak-proof containers.

This medicinal p roduct contains genetically modified human blood cells. Healthcare professionals handling Aucatzyl must take appropriate precautions (wearing gloves, protective clothing and eye protection) to avoid potential transmission of infectious diseases.

Preparati on prior to administration

• Keep the infusion bag(s) in the metal cassette(s) and transfer Aucatzyl to the on -site controlled- access vapour phase of liquid nitrogen for storage ≤ -150 °C (until ready for thaw and administration).
• Time out of the vapour phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (it is recommended not to exceed 90 seconds).

Planning prior to Aucatzyl preparation The patient batch -specific RfIC and Dose Schedule Planner will be provided in the cryoshipper and via Scheduling Portal. Confirm the patient identifiers on RfIC and infusion bags match, Figure 1.

1. Ensure the patient’s BM assessment results are available (see SmPC section 4.2, Bone marrow assessm ent).

NOTE: The patient’s BM blast assessment results will be used to select the appropriate dosing regimen: High tumour burden dose regimen if the blast percentage is > 20% or inconclusive or Low tumour burden dose regimen if the blast percentage is ≤ 20%, see Figure 2 .

2. The Aucatzyl Dose Schedule Planner, provided with the RfIC, assists the determination of the appropriate dose regimen to be administered on day 1 (3 days (± 1 day) after the completion of lymphodepleting chemotherapy) and day 10 (± 2 day s). Record the following information on the Dose Schedule Planner: a. The blast percentage from the patient’s BM assessment. b. The Aucatzyl bag serial number(s); number of bag type required for each dose; and the specified volume to administer via syringe (for the 10 × 10 6 dose) transcribed from the RfIC.

3. The completion of the Aucatzyl Dose Schedule Planner will guide the treating physician on the number of bags and the respective dose required, and the preparation of Aucatzyl for the day 1 and day 10 (± 2 days ) dose. The RfIC provides more information and is located inside the lid of the cryoshipper.

Transfer and thawing

• Using the completed Dose Schedule Planner for guidance transfer ONLY the cassette(s) / infusion bag(s) required for the given dosing day from the on-site vapour phase liquid nitrogen storage to an appropriate transfer vessel (i.e., a vapour phase liquid nitrogen cryoshipper, maintaining temperature ≤ -150 °C) for transport to the bag thaw location.

58 • Transfer the required cassettes one by one, confirming the Aucatzyl bag serial numbers and patient identifiers on each infusion bag label, see Figure 1.

• Time out of the vapour phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (it is recommended not to exceed 90 seconds).
• If more than one infusion bag has been required on a given dosing day, thaw one infusion bag at a time. Do NOT remove subsequent bags from the vapour phase liquid nitrogen storage (≤ -150 °C) until infusion of the previous bag is complete.
• Leave the Aucatzyl infusion bag in its overwrap, thaw at 37 °C using a water bath or dry thaw metho d until there are no visible frozen clumps left in the bag. Each bag should be gently massaged until the cells have just thawed. Thawing of each infusion bag between 2 to 8 minutes. Remove from the water bath or thaw device immediately after thawing is com plete.

Carefully remove the infusion bag from the overwrap taking care to avoid damage to the bag and ports.

• Gently mix the contents of the bag to disperse clumps of cellular material and administer immediately to the patient.
• Do not refreeze or refrigerate thawed product.

Infusion instructions Aucatzyl is for autologous and intravenous use only. For premedication and availability of tocilizumab or suitable alternative anti -IL-6 therapy (e.g., siltuximab) see SmPC section 4.2.

The patient’s identity mu st match the patient identifiers on the Aucatzyl Release for Infusion Certificate (RfIC) and infusion bag.

Dose administration for 10 × 10 6 CD19 CAR -positive viable T cells (syringe- based infusion) The 10 × 10 6 cell dose should be administered via syrin ge as this is the only way to deliver the volume specified on the RfIC. Withdrawal of the 10 × 106 dose into the syringe should be carried out as follows:

• Prepare and administer Aucatzyl using aseptic technique.
• Gently mix the contents of the bag to dispe rse clumps of cellular material.
• The volume to be administered for the 10 × 10 6 dose is specified on the RfIC.
• Use the smallest Luer -lock tip syringe necessary (1, 3, 5, or 10 mL) with a Luer -lock bag spike to draw up the volume specified on the RfIC. o Do NOT use a leukodepleting filter. o Do NOT use the syringe to mix the cells, see Figure 3 .

59 Figure 3: Syringe infusion guidance for 10 × 106 dose

• Prime the tubing with sodium chloride 9 mg/mL (0.9%) solution for injection prior to infusion.
• Once Aucatzyl has been drawn into the syringe, verify the volume and administer as an intravenous infusion (as a slow push approximately 0.5 mL/minute) through a central venous line (or large peripheral venous access line appropriate for blood products).
• Complete infusion at room temperature within 60 minutes post -thaw and flush the tubing line with 60 mL of sodium chloride 9 mg/mL (0.9%) solution for injection.
• Dispose of any unused portion of Aucatzyl (according to local biosafety guidelines).

D ose administration for 100 × 106 and/or 300 × 106 CD19 CAR- positive viable T cells

• Refer to the RfIC and the Dose Schedule Planner for the following details: o T he volume and total CD19 CAR-positive viable T cell number contained in each infusion bag. o The dose to be administered on the given dosing day and the number of bags required to deliver the specified CD19 CAR- positive viable T cell dose. o If more than one bag is needed, thaw subsequent bag after the previous bag is fully administered.
• Prime the tubing with sodium chloride 9 mg/mL (0.9%) solution for injection prior to infusion.
• Administer Aucatzyl via a gravity or peristaltic pump assisted intravenous infusion through a central venous line (or large peripheral venous access line appropriate for blood products). o Do NOT use a leukodepletin g filter. o Aseptic techniques must be applied when performing a venepuncture, spiking the ports, and through cell administration process. o Gently mix the contents of the bag during Aucatzyl infusion to disperse cell clumps. o Infuse the entire content of the Aucatzyl infusion bag at room temperature within 60 minutes post-thaw using a gravity or peristaltic pump. After the entire contents of the infusion bag is infused, rinse the bag with 30 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, then flush the tubing line with 60 mL of sodium chloride 9 mg/mL (0.9%) solution for injection. o Repeat steps 1 -3 for any additional infusion bags required on the given dosing day. Do Not initiate thaw of the next bag until infusion of the previous bag is compl ete.

60 Monitoring

• Patients should be monitored daily for 14 days after the first infusion for signs and symptoms of potential CRS, ICANS and other toxicities.
• Frequency of monitoring after the first 14 days should be carried out at the physician’s discret ion and should be continued for at least 4 weeks after infusion.
• Instruct patients to remain within close proximity of the qualified treatment centre (within 2 hours of travel) for at least 4 weeks following the first infusion.

Measures to take in case of acci dental exposure In case of accidental exposure local guidelines on handling of human- derived material must be followed. Work surfaces and materials which have potentially been in contact with Aucatzyl must be decontaminated with appropriate disinfectant.

Precautions to be taken for the disposal of the medicinal product Unused medicinal product and all material that has been in contact with Aucatzyl (solid and liquid waste) must 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 Aucatzyl (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/25/1951).

⚠️ 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.