Ebvallo

Package leaflet: Information for the patient

Ebvallo 2.8 × 10 - 7.3 × 10 cells/mL dispersion for injectable preparation

tabelecleucel (EBV-specific viable T cells)
This medicinal product is subject to additional monitoring. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while receiving this medicine. See the end of section 4 for information on how to report side effects.
Please 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 questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What Ebvallo is and what it is used for

Ebvallo contains the active substance tabelecleucel.
Tabelecleucel is an allogeneic T-cell immunotherapy. It is called allogeneic immunotherapy because
the blood cells used to produce this medicine come from human donors who are unrelated to the patient being treated.
Ebvallo is manufactured in the laboratory from T cells (a type of white blood cells) of a healthy donor who is immune to the Epstein-Barr virus.
These cells are selected to be compatible with the specific patient receiving Ebvallo. Ebvallo is administered by intravenous infusion.
Ebvallo is used to treat a rare type of tumour called Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD) in adult and paediatric patients aged 2 years and older.
Some people develop this disease months or years after having undergone a transplant. Before being treated with Ebvallo, patients will have previously been treated with other medicines (such as monoclonal antibodies or chemotherapeutic agents).

2. What you should know before being given Ebvallo

Do not receive Ebvallo

• if you are allergic to tabelecleucel or to any of the components of this medicine (listed in section 6). If you think you are allergic, consult your doctor.

Warnings and precautions
Talk to your doctor or nurse before receiving Ebvallo if:

• you have undergone a solid organ or bone marrow transplant, so that your doctor can monitor for signs and symptoms of transplant rejection.
• you are 65 years of age or older, so that your doctor can monitor you for possible serious side effects. Ebvallo should be used with caution in elderly patients.

Talk to your doctor or nurse after receiving Ebvallo if:

• you experience signs and symptoms of tumor flare reaction. Depending on the tumor location, Ebvallo may cause a side effect called tumor flare reaction. The tumor or enlarged lymph nodes may suddenly become painful or increase in size and could cause problems to organs near the tumor. This reaction usually occurs within the first few days after administration of Ebvallo. Your doctor will monitor you after the first doses to check whether the tumor or lymph node is growing and causing complications. Your doctor may prescribe additional medicines to treat or prevent tumor flare reaction.
• you experience signs and symptoms of graft-versus-host disease (GvHD). These symptoms include skin rash, changes in liver enzyme levels in the blood, yellowing of the skin, nausea, vomiting, diarrhea, and blood in the stool.
• you experience 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 experience signs and symptoms of a serious immune reaction called immune effector cell-associated neurotoxicity syndrome (ICANS), such as reduced level of consciousness, confusion, seizures, and cerebral edema.
• you experience signs and symptoms related to infusion reactions, such as fever.

An excipient in 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 to exclude the presence of infectious agents; however, there remains a minimal risk of infection. Your doctor or nurse will monitor you for signs and symptoms of infection and will prescribe treatment as needed.
After treatment with Ebvallo, you must not donate blood, organs, tissues, or cells.

Other medicines and Ebvallo
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Before receiving Ebvallo, inform your doctor or nurse if you are taking medicines such as chemotherapy agents or corticosteroids. If you are taking chemotherapy agents, these medicines may affect the efficacy of Ebvallo. If you are taking corticosteroids, your doctor may reduce the corticosteroid dose.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before receiving this medicine. This is because the effects of this medicine in pregnant or breastfeeding women are unknown and it may harm the fetus or breastfed infant. Ebvallo is not recommended during pregnancy or in women who may become pregnant and who are not using contraception.

• If you become pregnant or think you might be pregnant after starting treatment with Ebvallo, contact your doctor immediately.
• Discuss the need for contraception with your doctor.
• Talk to your doctor if you are breastfeeding or planning to breastfeed. Your doctor will help you decide whether to discontinue breastfeeding or discontinue Ebvallo, considering the benefits of breastfeeding for the infant and the benefits of Ebvallo for the mother.

Driving and using machines
Ebvallo has minimal influence on the ability to drive or operate machinery. If you experience changes in thinking ability or level of attention after treatment with this medicine, do not drive or operate machinery and inform your doctor immediately.

Ebvallo contains sodium and dimethyl sulfoxide (DMSO)
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., it is essentially “sodium-free”.
This medicine contains 100 mg of DMSO per mL. See section 2 “Warnings and precautions”.

3. How Ebvallo is administered

Ebvallo will always be administered to you by a doctor or nurse at a qualified treatment centre.
The doctor or nurse will give you Ebvallo as an intravenous injection. Each injection usually takes between 5 and 10 minutes.
Each treatment cycle lasts 35 days. You will receive 1 injection per week for 3 weeks, followed by approximately 2 weeks of observation to assess whether more than one cycle is needed. Your doctor will decide the number of cycles you will receive based on how your disease responds to Ebvallo.
Before you are given Ebvallo
The doctor or nurse will monitor your vital signs before each injection.
After you have been given Ebvallo
The doctor or nurse will monitor your vital signs, including blood pressure, for about 1 hour after the injection.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Serious side effects
Contact your doctor immediately if you experience any of the following side effects after receiving Ebvallo:

• Tumor flare reaction with symptoms such as shortness of breath, changes in thinking ability and level of alertness, pain at the tumor site, swollen and painful lymph nodes at the tumor site, mild fever.
• Graft-versus-host disease (GvHD) with symptoms such as skin rash, changes in liver enzyme levels in the blood, yellowing of the skin, nausea, vomiting, diarrhoea and blood in the stools.

Other possible side effects
Very common (may affect more than 1 in 10 people)

• Fever
• Diarrhoea
• Fatigue
• Feeling unwell (nausea)
• Low levels of red blood cells (anaemia)
• Reduced appetite
• Decreased sodium levels in the blood
• Abdominal pain or discomfort
• Decrease in white blood cell counts (including neutrophils)
• Increased liver enzyme levels in the blood
• Constipation
• Increased levels of alkaline phosphatase enzyme in the blood
• Decreased oxygen levels
• Dehydration
• Low blood pressure
• Nasal congestion
• Skin rash which may be red, irregular or filled with pus

Common (may affect up to 1 in 10 people)

• Dizziness
• Headache
• Low levels of magnesium, potassium or calcium in the blood
• Itching
• Chills
• Decrease in white blood cells (lymphocytes) in the blood
• Decrease in white blood cells (neutrophils) with fever
• Muscle weakness
• Joint pain, swelling and stiffness
• Increased creatinine levels in the blood
• Wheezing
• Confusion and disorientation
• Back pain
• Muscle pain
• Infection of the nose and throat
• Chest pain
• Increased lactic dehydrogenase levels in the blood
• Inflammation of the colon
• Pain
• Decrease in platelet count in the blood
• Abdominal swelling
• Delirium
• Reduced level of consciousness
• Hot flushes
• Inflammation of the lungs
• Drowsiness
• Rapid heartbeat
• Pain at the tumour site
• Decreased fibrinogen levels in the blood (a protein involved in blood clotting)
• Flatulence
• Swellings
• Skin ulcer
• Blue colour of the skin due to low oxygen levels
• Difficult or painful defecation
• Deterioration in general physical health
• Numbness, tingling or burning sensation in the hands and feet
• Pulmonary haemorrhage
• Change in skin colour
• Skin infection
• Destruction of soft tissue
• Persistent cough

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ebvallo

The doctor, pharmacist, or nurse is responsible for the storage of this medicinal product and for the proper disposal of unused product. The following information is intended exclusively for healthcare professionals.
Do not use this medicinal product after the expiry date. The expiry date is stated on the batch information leaflet and on the packaging.
Store Ebvallo frozen in liquid nitrogen vapour at a temperature of -150 °C or lower until thawing for use.
The medicinal product must be thawed and diluted within 1 hour after initiation of thawing. Administration must be completed within 3 hours after initiation of thawing.
After thawing and dilution are complete, store at a temperature between 15 °C and 25 °C. Protect the product from light. Do not refreeze. Do not irradiate.

6. Package contents and other information

What Ebvallo contains

• Ebvallo contains tabelecleucel at an approximate concentration of 2.8 × 10 to 7.3 × 10 cells/mL.
• The other components (excipients) are: dimethyl sulfoxide, human serum albumin, phosphate-buffered saline. See section 2 “Ebvallo contains sodium and dimethyl sulfoxide (DMSO)”.

Description of the appearance of Ebvallo and contents of the pack
Ebvallo is a translucent, injectable cell dispersion, colourless to slightly yellow.
Ebvallo is supplied in cartons containing 1 to 6 vials, depending on the dose required for the patient. Each vial contains 1 mL of this medicinal product.
Marketing Authorisation Holder
PIERRE FABRE MEDICAMENT
Les Cauquillous
81500 Lavaur
France
Manufacturer
PIERRE FABRE MEDICAMENT PRODUCTION
Parc industriel de la Chartreuse
81100 Castres
France
An authorisation has been granted to this medicinal product under “exceptional circumstances”. This means that, due to the rarity of the disease, it has not been possible to obtain complete information about this medicinal product.
The European Medicines Agency will review annually any new information on this medicinal product and this package leaflet will be updated if necessary.
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

The following information is intended for healthcare professionals only:

It is important to read the entire content of this procedure before administering Ebvallo.
Precautions to be taken before handling or administering the medicinal product

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

Preparation prior to administration

• The patient’s identity must match the patient identifiers (PFPIN and institute patient ID) listed on the attached Ebvallo batch information sheet and on the packaging. Product-patient reconciliation must be performed by matching information on the batch information sheet with 1) the packaging (comparing PFPIN and FDP numbers) and with 2) the vial label (comparing batch numbers and donor ID). Do not prepare or administer Ebvallo if patient identity or product-patient reconciliation cannot be confirmed. Before thawing, ensure that required dose calculations have been completed, all necessary materials for dose preparation are available, and the patient is present and has been clinically assessed.

Dose calculations

• For information on cell concentration per vial, refer to the attached batch information sheet and packaging.
• Note: The concentration of viable T cells listed on the batch information sheet and packaging is the actual concentration of each vial. This may differ from the nominal concentration stated on the vial label, which must not be used for dose preparation calculations. Each vial contains at least 1 mL of deliverable volume.

Preparation of diluent

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

Thawing

• The thawing process for Ebvallo may begin when the patient is present in the hospital and has been clinically evaluated.
• Remove the packaging from liquid nitrogen vapours at ≤ -150 °C.
• During thawing, frozen Ebvallo vials must be placed inside a sterile bag to protect them from contamination and thawed in an upright position in a 37 °C water bath or in a dry thawing device.
• Record the start time of thawing. While the medicinal product is thawing, gently rotate the product vial until complete thawing is visually confirmed (approximately 2.5–15 minutes). The product must be removed from the thawing device immediately after thawing is complete.
• Dose preparation must be completed within one hour of the start of thawing.
• Thawed or prepared product must not be refrozen. Do not irradiate.

Dilution and dose preparation

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

Administration

• Administer Ebvallo as a single intravenous dose after dilution.
• Connect the final medicinal product syringe to the patient’s intravenous (IV) catheter and inject over 5–10 minutes.
• Once Ebvallo has been fully delivered from the syringe, 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 must be followed, which may include washing contaminated skin and removing contaminated clothing. Work surfaces and materials that have potentially come into contact with Ebvallo must be decontaminated with an appropriate disinfectant.

Precautions for disposal of the medicinal product
Unused medicinal product and all materials that have come into contact with Ebvallo (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines for handling human-derived material.