EBVALLO 2.8 × 10⁷ - 7.3 × 10⁷ CELLS/ML INJECTABLE DISPERSION

Introduction

Package Leaflet: Information for the Patient

Ebvallo 2.8 × 107- 7.3 × 107cells/ml injectable suspension

tabelecleucel (EBV-specific viable T cells)

This medicine is subject to additional monitoring, which will allow for quicker identification of new safety information. You can help by reporting any side effects you may get. The last section of the package leaflet contains information on how to report side effects.

Read all of this leaflet carefully before you start using 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, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Ebvallo and what is it used for

Ebvallo contains the active substance tabelecleucel.

Tabelecleucel is an allogenic immunotherapy with T cells. It is called allogenic immunotherapy because the blood cells used to make this medicine come from human donors who are not related to the patient 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 the patient receiving Ebvallo. Ebvallo is given by injection into a vein.

Ebvallo is used to treat a rare type of cancer called post-transplant lymphoproliferative disorder (PTLD) associated with the Epstein-Barr virus (EBV+ PTLD) in adults and children from 2 years of age. Some people develop this disease months or years after receiving a transplant. Patients will have received treatment with other medicines for this disease, such as monoclonal antibodies or chemotherapy, before receiving 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

Tell 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 used with caution in elderly patients.

Tell your doctor or nurse after you are given Ebvallo if:

• you have signs and symptoms of tumor flare reaction. Depending on the location of the tumor, Ebvallo may cause a side effect called tumor flare reaction. The tumor or enlarged lymph nodes may become suddenly painful or enlarged and may cause problems in the organs near the tumor. Tumor flare reaction usually occurs in the first few days after receiving Ebvallo. Your doctor will monitor you after the first doses to see if the tumor or lymph nodes may grow large enough to cause problems. Your doctor may give you other medicines to treat or prevent tumor flare reaction.

• you have signs and symptoms of graft-versus-host disease (GVHD), such as skin rash, altered liver enzymes in blood, yellowing of the skin, nausea, vomiting, diarrhea, and bloody stools.

• you have signs and symptoms of a severe immune reaction called cytokine release syndrome (CRS), such as fever, chills, low blood pressure, and difficulty breathing.

• you have signs and symptoms of a severe immune reaction called immune effector cell-associated neurotoxicity syndrome (ICANS), such as decreased level of consciousness, confusion, seizures, and brain inflammation.

• you have signs and symptoms of infusion-related reactions, such as fever.

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

Ebvallo is tested for the presence of infectious microbes, but there is a small risk of infection. Your doctor or nurse will monitor you for signs and symptoms of infections and provide treatment when necessary.

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 any medicines, such as chemotherapy or corticosteroids. If you are receiving chemotherapy, this medicine may affect the efficacy of Ebvallo. If you are taking corticosteroids, your doctor should 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 on pregnant or breast-feeding women are not known, and it may harm the fetus or baby. Ebvallo is not recommended during pregnancy and in women who may become pregnant and are not using contraception.

• If you are pregnant or think you may be pregnant after you have started treatment with Ebvallo, tell your doctor immediately.
• Talk to your doctor about the need for contraception.
• If you are breast-feeding or plan to breast-feed, ask your doctor for advice. Your doctor will help you decide whether to stop breast-feeding or stop Ebvallo treatment, considering the benefit of breast-feeding to the child and the benefit of Ebvallo to the mother.

Driving and using machines

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

Ebvallo contains sodium and dimethyl sulfoxide (DMSO)

This medicine contains less than 1 mmol of sodium (23 mg) per ml, which is essentially ‘sodium-free’.

This medicine contains 100 mg of 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 center.

Your doctor or nurse will give you Ebvallo into a vein. This usually takes between 5 and 10 minutes per injection.

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

Before you are given Ebvallo

Your doctor or nurse will check your vital signs before each injection.

After you are given Ebvallo

Your doctor or nurse will check your vital signs, including blood pressure, for 1 hour after 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 experience any of the following side effects after receiving Ebvallo.

• Tumor flare reaction with symptoms such as difficulty breathing, changes in thinking or level of alertness, pain in the tumor area, sensitive and inflamed lymph nodes in the tumor area, low-grade fever.
• Graft-versus-host disease (GVHD), with symptoms such as skin rash, altered liver enzymes in blood, yellowing of the skin, nausea, vomiting, diarrhea, and bloody stools.

Other possible side effects

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

• Fever
• Diarrhea
• Fatigue
• Nausea
• Low red blood cell count (anemia)
• Decreased appetite
• Low sodium levels in the blood
• Abdominal pain or discomfort
• Decreased white blood cell count (including neutrophils)
• Increased liver enzymes in the blood
• Constipation
• Increased alkaline phosphatase levels in the blood
• Low oxygen levels
• Dehydration
• Low blood pressure
• Nasal congestion
• Skin rash, possibly red, with bumps or pus

Common (may affect up to 1 in 10 people)

• Dizziness
• Headache
• Low magnesium, potassium, or calcium levels in the blood
• Itching
• Chills
• Decreased white blood cell count (lymphocytes)
• Decreased white blood cell count (neutrophils) with fever
• Muscle weakness
• Joint pain, swelling, and stiffness
• Increased creatinine levels in the blood
• Wheezing
• Confusion and disorientation
• Back pain
• Muscle pain
• Nose and throat infection
• Chest pain
• Increased lactate dehydrogenase levels in the blood
• Colon inflammation
• Pain
• Decreased platelet count in the blood
• Gas
• Delirium
• Decreased level of consciousness
• Hot flashes
• Lung inflammation
• Somnolence
• Fast heart rate
• Tumor pain
• Decreased fibrinogen levels in the blood (a protein involved in clot formation)
• Flatulence
• Swelling
• Skin ulcer
• Blue discoloration of the skin due to low oxygen levels
• Difficulty or pain when defecating
• General deterioration
• Numbness, tingling, or burning sensation in the hands or feet
• Bleeding in the lungs
• Discoloration of the skin
• Skin infection
• Soft tissue destruction
• Persistent cough

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through 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. Storage of Ebvallo

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

Do not use this medicine after the expiry date. The expiry date is stated on the batch leaflet (BL) and on the packaging.

Store Ebvallo frozen in liquid nitrogen in the vapor phase at a temperature of -150°C or lower until it is thawed for use.

The medicine must be thawed and diluted within 1 hour of starting thawing. Administration must be completed within 3 hours of starting thawing.

Store between 15°C and 25°C after completion of thawing and dilution. Protect the product from light. Do not re-freeze. Do not irradiate.

6. Container Contents and Additional Information

Composition of Ebvallo

• Ebvallo contains tabelecleucel at an approximate concentration of 2.8 × 10^7 - 7.3 × 10^7 cells/ml.
• The other components (excipients) are dimethyl sulfoxide, human serum albumin, and phosphate-buffered saline solution. See section 2 "Ebvallo contains sodium and dimethyl sulfoxide (DMSO)".

Appearance of Ebvallo and Container Contents

Ebvallo is a translucent, colorless to slightly yellowish cellular dispersion for injection.

Ebvallo is supplied in individual containers for each patient, containing between 1 vial and 6 vials, depending on the patient's specific required dose. Each vial contains 1 ml of the medication.

Marketing Authorization Holder

PIERRE FABRE MEDICAMENT

Les Cauquillous

81500 Lavaur

France

Manufacturer

PIERRE FABRE MEDICAMENT PRODUCTION

Parc industriel de la Chartreuse

81100 Castres

France

Date of Last Revision of this Leaflet:

This medication has been authorized under "exceptional circumstances". This approval means that due to the rarity of this disease, it has not been possible to obtain complete information on this medication.

The European Medicines Agency will review any new information on this medication that may become available annually, and this leaflet will be updated as necessary.

Other Sources of Information

Detailed information on this medication is available on the European Medicines Agency website: https://www.ema.europa.eu.

This information is intended for healthcare professionals only:

It is essential that you read the entire content of this procedure before administering Ebvallo.

Precautions to be taken before handling or administering the medication

• This medication contains human blood cells. Healthcare professionals handling Ebvallo must take adequate precautions (wearing gloves and goggles) to avoid potential transmission of infectious diseases.

Pre-administration preparation

• The patient's identity must match the patient identifiers (PFPIN and institution patient identification) listed on the Ebvallo batch information leaflet (HIL) and on the container. Product-patient reconciliation must be performed by comparing the HIL information with 1) the container (matching PFPIN and FDP number) and with 2) the vial label (matching batch number and donor identification). Do not prepare or administer Ebvallo if the patient's identity or product-patient reconciliation cannot be confirmed. Before thawing, ensure that the required dose calculations have been completed, that all necessary materials for preparing the dose are available, and that the patient is at the administration site and has been clinically evaluated.

Dose calculation

• Refer to the batch information leaflet (HIL) attached to the carton for information on the cell concentration per vial.
• Note: The concentration of viable T cells listed on the HIL and container is the actual concentration of each vial. It may differ from the nominal concentration listed on the vial label, which must not be used to calculate dose preparation. Each vial contains 1 ml of administrable volume.

Prepare the diluent

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

Thawing

• The Ebvallo thawing process can begin after the patient is at the site and has been clinically evaluated.
• Remove the storage container supplied with liquid nitrogen in the vapor phase at ≤ -150 °C.
• The frozen Ebvallo vial(s) must be placed inside a sterile bag during thawing to protect it from contamination and thawed in a vertical position in a 37°C water bath or dry thawing chamber.
• Record the start time of thawing. While the medication is thawing, gently agitate the product vial(s) until completely thawed by inspection (approximately 2.5 to 15 minutes). The product must be removed from the thawing device immediately after completing thawing.
• Dose preparation must be completed within 1 hour from the start of thawing.
• The thawed or prepared product must not be re-frozen. Do not irradiate.

Dilution and dose preparation

• Gently invert the vial(s) until the cellular dispersion is mixed.
• Aseptically withdraw the required volume of cellular dispersion from the product vial(s) to the product extraction syringe using an 18-gauge non-filtered needle.
• Aseptically transfer the cellular dispersion from the product extraction syringe to the dosing syringe (previously filled with diluent). Ensure that all contents of the product extraction syringe are transferred.
• Inspect the diluted Ebvallo in the dosing syringe: the dose cellular dispersion should appear as a translucent, turbid solution. If visible clumps appear, continue gently mixing the solution. Small clumps of cellular material should disperse with gentle manual mixing.
• Maintain Ebvallo between 15°C and 25°C during dose preparation and administration. Dose preparation must be completed within 1 hour from the start of thawing. Administration must be completed within 3 hours from the start of thawing.

Administration

• Administer Ebvallo as a single dose by intravenous infusion after dilution.
• Connect the medication syringe to the patient's intravenous catheter and inject over 5 to 10 minutes.
• Once the syringe has delivered all the Ebvallo, flush the intravenous line with ≥ 10 ml of 9 mg/ml (0.9%) sodium chloride injectable solution.

Measures to be taken in case of accidental exposure

In case of accidental exposure, local guidelines for handling human-derived material should be followed, which may include washing contaminated skin and removing contaminated clothing. Work surfaces and materials that may have come into contact with Ebvallo should be decontaminated with a suitable disinfectant.

Precautions to be taken for medication disposal

Unused medication and all materials that have come into contact with Ebvallo (solid and liquid waste) should be handled and disposed of as potentially infectious waste in accordance with local regulations on handling human-derived material.