InfoCons Consumer Protection informs you – Ebvallo – 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.
• If you have any further questions, ask your doctor or nurse.
• 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.

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

Ebvallo contains the active substance tabelecleucel.

Tabelecleucel is a n allogeneic T -cell immunotherapeutic . It is called an allogeneic immuno therap eutic because the blood cells used to make th is medicine come from human donors who are not related to the patient who is being treated. Ebvallo is made in a laboratory from T cells (a type of white blood cell) from a healthy donor who is immune to the Epstein- Barr virus. These cells have been individually selected to match with the patient receiving Ebvallo. Ebvallo is given as an injection into a vein.

Ebvallo is used to treat a rare kind of cancer called Epstein -Barr v irus positive post -transplant lymphoproliferative disease (EBV + PTLD) for adult s and children 2 years of age and older . Some people experience this condition months or years after they have had a transplant. Patients will have received treatment with other medicines for this condition, such as monoclonal antibodies or chemotherapy, before they are given Ebvallo.

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

You must not be given Ebvallo

• if you are allergic to tabelecleucel or any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, ask your doctor for advice.

Warnings and precautions

Talk to your doctor or nurse before you are given Ebvallo if:

• you have had a solid organ transplant or bone marrow transplant , so your doctor can monitor you for signs and symptoms of transplant rejection.
• you are 65 years of age or older, so your doctor can monitor you for serious side effects.

Ebvallo should be use d with caution in elderly patients .

Talk to your doctor or nurse after you are given Ebvallo if :

• you have signs and s ymptoms of tumour flare reaction. Depending on the location of the tumo ur, Ebvallo can cause a side effect called tumo ur flare reaction. The tumour or enlarged lymph nodes may become suddenly painful or increase in size and could cause problems for organs next to the tumour. Tumo ur flare reaction generally occurs in the first few days after receiving Ebvallo. Your doctor will monitor you after the first few doses to see if your tumour or lymph node could get big enough to cause problems. Your doctor may give you other medicines to treat/prevent tumour flare reaction .
• you have signs and symptoms of graft -versus -host disease ( GvHD) , such symptoms include skin rash, abnormal liver enzymes in the blood, yellowing of the skin, nausea, vomiting, diarrhoea and bloody stools.
• you have signs and symptoms of a serious immune reaction called cytokine release syndrome (CRS) , such as fever, chills, low blood pressure and shortness of breath.
• you have signs and symptoms of a serious immune reaction called immune effector cell -associated neurotoxicity syndrome (ICANS), such as depressed level of consciousness, confusion, seizures and swelling of the brain.
• you have signs and symptoms of infusion- related reactions, such as fever.

An ingredient of Ebvallo called dimethyl sulfoxide (DMSO) may cause an allergic reaction. Your doctor or nurse will monitor you for signs and symptoms of a n allergic reaction. See section 2 “Ebvallo contains sodium and dimethyl sulfoxide (DMSO)”.

Ebvallo is test ed for the presence of infectious microbes , but a small risk of in fection remains . Your doctor or nurse will mon itor you for signs and symptoms of infections and provide treatment as needed .

After treatment with Ebvallo, you must not donate blood, organs, tissues or cells.

Other medicines and Ebvallo

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

Before you are given Ebvallo, tell your doctor or nurse if you are taking medicines such as chemotherapy or corticosteroids . If you are taking chemotherapy, this medicine may affect how well Ebvallo works. If you are taking corticosteroids , your doctor will reduce the dose of corticosteroids .

Pregnancy, breast -feeding and fertility 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 you are given this medicine. This is because the effects of this medicine in pregnant or breast -feeding women are not known, and it may harm your unborn baby or your breast -fed child. Ebvallo is not recommended during pregnancy and in women who could become pregnant not using contraception.

• If you are pregnant or think you may be pregnant after you have started treatment with Ebvallo , talk to your doctor immediately.
• Discuss the need for contraception with your doctor.
• Tell your doctor if you are breast -feeding or plan to do so. Your doctor will then help you decide whether to stop breast -feeding or whether to stop taking Ebvallo, considering the benefit of breast – feeding the baby and the benefit of Ebvallo to the mother.

Driving and using machines

Ebvallo has minor influence on the ability to drive or use machines. I f you experience changes in your thinking or level of alertness after being treated with this medicine , do not drive or operate machines and tell your doctor immediately.

Ebvallo contains sodium and dimethyl sulfoxide (DMSO)

This medicine contains less than 1 mmol sodium (23 mg) per vial , that is to say essentia lly ‘sodium – free’.

This medicine contains 100 mg DMSO per mL. See Section 2 “Warnings and precautions ”.

💊 3. How Ebvallo is given

Ebvallo will always be given to you by a doctor or nurse in a treatment centre.

Your doctor or nurse will give you Ebvallo by injection into a vein. This usually takes 5 to 10 minutes for each injection .

Each cycle of treatment consists of 35 days. You will be given 1 injection per week for 3 weeks, followed by approximately 2 weeks of observation to see if you will need more than one cycle. Your doctor will decide the number of cycles you will receive based on how your disease responds to Ebvallo.

Before you are given Ebvallo Your doctor or nurse will monitor your vital signs prior to each injection.

After you are given Ebvallo Your doctor or nurse will monitor your vital signs, including blood pressure, for about 1 hour following the injection.

❗ 4. Possible side effects

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

Serious side effects

Tell your doctor immediately if you get any of the following side effect s after receiving Ebvallo :

• Tumour flare reaction with symptoms such as shortness of breath, changes in your thinking or level of alertness, pain at the tumour site, tender swollen lymph nodes at the tumour site, low grade fever
• Graft -versus- host disease (GvHD) with symptoms such as skin rash, abnormal liver enzymes in the blood, yellowing of the skin, nausea, vomiting, diarrhoea and bloody stools Other possible side effects

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

• Fever
• Diarrhoea
• Tiredness
• Feeling sick (n ausea )
• Low level s of red blood cells ( anaemia)
• Decreased appetite
• Decreased levels of sodium in the blood
• Abdominal pain or discomfort
• Decreased number of white blood cells (including neutrophils)
• Increased liver enzymes in the blood
• Constipation
• Increased level s of the enzyme alkaline phosphatase in the blood
• Decreased oxygen levels
• Dehydration
• Low blood pressure
• Stuffy nose
• Skin rash which may be red, bumpy or pus -filled

Common (may affect up to 1 in 10 people)

• Dizziness
• Headache
• Decreased levels of magnesi um, potassium or calcium in the blood
• Itching
• Chills
• Decreased number of white blood cells (lymphocytes)
• Decreased number of white blood cells (neutrophils) with fever
• Muscular weakness
• Joint pain, swelling and stiffness
• Increased levels of creatinine in the blood
• Wheezing
• Confusion and disorientation
• Back pain
• Muscle pain
• Nose and throat infection
• Chest pain
• Increased levels of lactate dehydrogenase in the blood
• Inflammation of the colon
• Pain
• Decreased number of platelets in the blood
• Bloating
• Delirium
• Depressed level of consciousness
• Hot flush
• Inflammation of the lungs
• Sleepiness
• Fast heartbeat
• Tumour pain
• Decreased level s of fibrinogen in the blood (a protein involved in blood clotting)
• Flatulence
• Swelling
• Skin ulcer
• Blue skin colour due to low oxygen levels
• Difficult or painful bowel movement
• General physical health deterioration
• Numbness, tingling or burning sensation in hands or feet
• Bleeding in the lungs
• Skin discolouration
• Skin infection
• Destruction of soft tissue
• Persistent cough

Reporting of side effects

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 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 Ebvallo

Your doctor, pharmacist or nurse is responsible for storing this medicine and disposing of any unused product correctly. The following information is intended for healthcare professionals.

Do not use this medicine after the expiry date. The expiry date is provided on the Lot Information Sheet (LIS) and carton.

Store Ebvallo frozen in the vapour phase of liquid nitrogen at – 150 ° C or below until thawed for use.

The medicin e should be thawed and diluted within 1 hour from the start of thaw . Administration must be completed within 3 hours from the start of thaw .

Store between 15 °C to 25 °C after thawing and dilution are complete. Protect product from light. Do not refreeze. Do not irradiate.

📦 6. Contents of the pack and other information

What Ebvallo contains

• Ebvallo contains tabelecleucel at a n approximate concentration of 2.8 × 10 7 – 7.3 × 107 cells/ mL.
• The other ingredients (excipients) are: d imethyl sulfoxide, human serum albumin, phosphate

buffered saline . See section 2 “Ebvallo contains sodium and dimethyl sulfoxide (DMSO )”.

What Ebvallo looks like and contents of the pack

Ebvallo is a translucent, colourless to slightly yellow cell dispersion for injection.

Ebvallo is provided in individual patient cartons containing 1 vial to 6 vials according to the patient – specific dose required . Each vial contains 1 mL of this medicine .

Marketing Authorisation Holder

PIERRE FABRE MEDICAMENT Les Cauquillous 81500 Lavaur France

Manufacturer

PIERRE FABRE MEDICAMENT PRODUCTION Parc industriel de la Chartreuse 81100 Castres France

This leaflet was last revised i n

This medicine has been authorised under ‘exceptional circumstances’. This means that because of the rarity of this disease, it has been impossible to get complete information on this medicine. The European Medicines Agency will review any new information on this medicine every year and this leaflet will be updated as necessary.

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu . ————————————————————————————————————————

🩺 Information intended for healthcare professionals only

It is important that you read the entire content of this procedure prior to administering Ebvallo.

Precautions to be taken before handling or administering the medicinal product

• This medicinal product contains human blood cells. Healthcare professionals handling Ebvallo must take appropriate precautions (wearing gloves and glasses) to avoid potential transmission of infectious diseases.

Preparation prior to administration

• The patient’s identity must match the patient identifiers (PFPIN and Institution Patient ID) on the accompanying Ebvallo Lot Information Sheet (LIS) and carton . Product -patient reconciliation must be performed by matching information on the LIS against 1) the carton (matching PFPIN and FDP Number) and against 2) the vial label (matching Lot Number and Donor ID) . Do not prepare or administer Ebvallo if the patient’s identi ty or the product -patient reconciliation cannot be confirmed . Prior to thawing, ensure that the required dose calculations are completed, all materials needed to prepare the dose are available, and the patient is onsite and has been clinically evaluated.

Dose calculations

• See the accompanying L ot Information S heet (LIS) and carton for information pertaining to the concentration of cells per vial.
• Note: The viable T -cell concentration on the LIS and carton is the actual concentration of each vial. This may be different than the nominal concentration listed on the vial label, which should not be used for dose preparation calculations. Each vial contains 1 mL deliverable volume .

Prepare the diluent

• Select the appropriate diluent volume (30 mL for patient weight ≤ 40 kg; 50 mL for patient weight > 40 kg) .
• Aseptically draw the selected volume of diluent into the dosing syringe .

Thaw ing

• The thawing process of Ebvallo can begin after the patient is onsite and has been clinically evaluated .
• Remove the carton from the vapour phase of liquid nitrogen at ≤ -150 °C.
• Frozen vial (s) of Ebvallo should be placed inside a sterile bag during thawing to protect from contamination and thawed upright in a 37 ° C water bath or dry thawing chamber.
• Record the start of thaw time. While the medicinal product thaws, swirl the product vial(s) gently until fully thawed by inspection (approximately 2.5 to 15 minutes). Product should be removed from the thawing device immediately upon completion of thaw.
• Dose preparation must be completed within 1 hour from the start of thaw.
• Thawed or prepared product must not be refrozen. Do not irradiate.

Dilution and dose p reparation

• Gently invert the vial (s) until the cell dispersion is mixed.
• Aseptically withdraw the required cell dispersion volume from the provided product vial (s) into the product draw syringe using an 18- gauge unfiltered needle.
• Aseptically transfer the cell dispersion from the product draw syringe to the dosing syringe (previously filled with diluent). Ensure entire content is transferred from the product draw syringe.
• Inspect the diluted Ebvallo in the dosing syringe: cell dispersion should appear as a translucent, hazy solution. If visible clumps appear , continue to gently mix the solution. Small clumps of cellular material should disperse with gentle manual mixing.
• Maintain Ebvallo between 15 °C to 25 ° C during dose preparation and administration. Dose preparation must be completed within 1 hour from the start of thaw. Administration must be completed within 3 hours from the start of thaw. Ebvallo contains 10% DMSO . Ebvallo should be injected to the patient as soon as possible after thawing.

Administration

• Administer Ebvallo as a single dose intravenously after dilution.
• Connect the final medicinal product syringe to the patient’s intravenous catheter and inject over 5 to 10 minutes.
• Once Ebvallo is fully dispensed from the syringe, flush the intravenous line with ≥ 10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection.

Measures to take in case of accidental exposure In case of accidental exposure, local guidelines on handling of human- derived material should be followed, which may include washing of the contaminated skin and removal of contaminated clothes.

Work surfaces and materials which have potentially been in contact with Ebvallo must be decontaminated with appropriate disinfectant.

Precautions to be taken for the disposal of the medicinal product Unused medicinal product and a ll material that has been in contact with Ebvallo (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 Ebvallo (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/22/1700).

⚠️ 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.