ABECMA 260-500 x 10e6 cells for infusion

Introduction

Package Leaflet: Information for the Patient

Abecma 260‑500×106cell dispersion for infusion

idecabtagene vicleucel (viable T‑CAR+ lymphocytes)

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

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.
• Your doctor will give you a patient information card. Read the card carefully and follow the instructions it contains.
• Always show the patient information card to your doctor or nurse when you see them or if you go to hospital.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Abecma and what is it used for

What is Abecma

Abecma is a type of medicine called “genetically modified cellular therapy”. The active substance of the medicine is idecabtagene vicleucel, which is made from your own white blood cells, called T lymphocytes.

What Abecma is used for

Abecma is used to treat adults with multiple myeloma, which is a cancer of the bone marrow.

It is given when previous treatments for your cancer have not worked or the cancer has come back.

How Abecma works

Your white blood cells are collected from your blood and genetically modified so that they can target the myeloma cells in your body.

When Abecma is infused into your blood, the modified white blood cells will attack the myeloma cells.

2. What you need to know before you are given Abecma

Do not receive Abecma

• if you are allergic to any of the other components of this medicine (listed in section 6). If you think you may be allergic, talk to your doctor.
• if you are allergic to any of the components of the medicines that will be given to you as lymphodepleting chemotherapy, which is used to prepare your body for treatment with Abecma.

Warnings and precautions

Before receiving Abecma, tell your doctor if:

• you have lung or heart problems.
• you have low blood pressure.
• you have had a stem cell transplant in the last 4 months.
• you have signs or symptoms of graft-versus-host disease. This disease occurs when the transplanted cells attack your own body and causes symptoms such as skin rash, nausea, vomiting, diarrhea, and blood in the stool.
• you have an infection. You will be treated for the infection before Abecma is given.
• you notice that your cancer symptoms are getting worse. For multiple myeloma, these can be fever, feeling weak, bone pain, or weight loss without any apparent reason.
• you have had an infection with cytomegalovirus (CMV), hepatitis B or C virus, or human immunodeficiency virus (HIV).
• you have been vaccinated in the last 6 weeks or are scheduled to receive a vaccine in the coming months.

If you are in any of these situations (or are unsure), talk to your doctor before you are given Abecma.

Patient treated with Abecma may develop new types of cancer. Cases have been reported of patients developing cancer, which starts from a type of white blood cell called T lymphocytes, after treatment with Abecma and similar medicines. Talk to your doctor if you experience any new swelling of the glands (lymph nodes) or changes in the skin, such as new rashes or lumps.

Tests and examinations

Before receiving Abecma, your doctor

• will examine your lungs, heart, and blood pressure.
• will look for signs of infection (any infection will be treated before Abecma is given).
• will check if your cancer is getting worse.
• will do a test to check for CMV, hepatitis B, hepatitis C, or HIV infection.

After receiving Abecma

• there are serious side effects that you should tell your doctor or nurse about straight away and which may need urgent medical attention. See “serious side effects” in section 4.
• your doctor will do regular blood tests to check your blood cell counts, as the number of blood cells may decrease.
• you should stay near the treatment center where you received Abecma for at least 4 weeks. See sections 3 and 4.
• do not donate blood, organs, tissues, or cells for transplantation.

Children and adolescents

Abecma must not be given to children or adolescents under 18 years of age.

Other medicines and Abecma

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription.

Medicines that affect the immune system

Before receiving Abecma, tell your doctor or nurse if you are taking medicines that weaken the immune system, such as corticosteroids. You should do this because these medicines may interfere with the effect of Abecma.

For information on the medicines that will be given to you before Abecma, see section 3.

Vaccinations

You must not receive certain vaccines, specifically live vaccines:

• in the 6 weeks before receiving a short course of chemotherapy (called lymphodepleting chemotherapy) that is given to prepare your body for Abecma.
• while being treated with Abecma.
• after treatment, while your immune system is recovering.

Talk to your doctor if you need to receive any vaccine.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, talk to your doctor before you are given this medicine. The effects of Abecma on pregnant or breastfeeding women are not known and may be harmful to the unborn baby or breastfed child.

• If you are pregnant or think you may be pregnant after treatment with Abecma, talk to your doctor straight away.
• A pregnancy test will be done before you start treatment. Abecma should only be given if the results show that you are not pregnant.

If you have received Abecma, talk to your doctor about pregnancy.

Driving and using machines

Do not drive, use machines, or take part in activities where you need to be alert for at least 8 weeks after treatment or until your doctor tells you that you have fully recovered. Abecma may cause drowsiness, confusion, or seizures (fits).

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

This medicine contains up to 752 mg of sodium (main component of cooking/table salt) per dose. This is equivalent to 37.6% of the maximum recommended daily intake of sodium for an adult.

This medicine contains up to 274 mg of potassium per dose, which should be taken into account in the treatment of patients with kidney problems or those on a low potassium diet.

If you have not been exposed to DMSO before, you should be closely monitored during the first few minutes of the infusion period.

3. How Abecma is given

Donation of blood to make Abecma from your white blood cells

• Your doctor will take blood from you through a line (catheter) that is put into a vein. Some of your white blood cells will be separated from the blood and the rest of the blood will be returned to your body. This procedure is called “leukapheresis” and may take 3 to 6 hours. You may need to have this procedure repeated.
• Your white blood cells will then be frozen and sent for Abecma to be made.

Other medicines that will be given to you before Abecma

• A few days before you receive Abecma, you will be given a short course of chemotherapy. The purpose of this is to remove your white blood cells.
• Just before you receive Abecma, you will be given paracetamol and an antihistamine. The purpose of these is to reduce the risk of infusion reactions and fever.

How Abecma is given

• Your doctor will check that Abecma has been made from your own blood by checking that the patient identification information on the labels of the medicine matches your details.
• Abecma is given into a vein through a line by intravenous infusion.

After Abecma is given

• You should stay near the treatment center where you received Abecma for at least 4 weeks.
• You may be followed daily at the treatment center for at least 10 days to check that the treatment is working and to treat any side effects you may have. See sections 2 and 4.
• Do not donate blood, organs, tissues, or cells for transplantation.

If you miss an appointment

Call your doctor or the treatment center as soon as possible to make another appointment.

4. Possible side effects

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

Serious side effects

Tell your doctor straight away if you experience any of the following side effects after treatment with Abecma. They usually occur in the first 8 weeks after infusion, but can also occur later:

Very common: may affect more than 1 in 10 people

• fever, chills, difficulty breathing, dizziness or fainting, nausea, headache, fast heart rate, low blood pressure, or fatigue. These can be symptoms of cytokine release syndrome (CRS), a serious and potentially life-threatening condition.
• any sign of infection, such as fever, chills, or shivering, cough, difficulty breathing, rapid breathing rate, or fast heart rate.
• severe tiredness or weakness or difficulty breathing, which can be signs of low red blood cell count (anemia).
• bleeding or bruising easily without cause, including nosebleeds or bleeding from the mouth or intestines, which can be a sign of low platelet count in the blood.

Common: may affect up to 1 in 10 people

• shaking, weakness with loss of movement on one side of the body, trembling, slow movements, or stiffness, which can be symptoms of parkinsonism.

Uncommon: may affect up to 1 in 100 people

• confusion, memory problems, difficulty speaking or slow speech, difficulty understanding language, unsteadiness or lack of coordination, disorientation, decreased level of consciousness, or excessive sleepiness, loss of consciousness, delirium, seizures (fits), which can be symptoms of a condition called immune effector cell-associated neurotoxicity syndrome (ICANS).

Tell your doctor straight away if you experience any of these side effects, as you may need urgent medical treatment.

Other possible side effects

Very common: may affect more than 1 in 10 people

• lack of energy
• high blood pressure
• decreased appetite
• constipation
• swelling of the ankles, arms, legs, and face
• joint pain
• difficulty sleeping
• low white blood cell count (neutrophils, leukocytes, and lymphocytes), which can increase the risk of infection
• infections, such as pneumonia or infections of the respiratory tract, mouth, skin, urinary tract, or blood, which can be caused by bacteria, viruses, or fungi
• blood test results showing low levels of antibodies, called immunoglobulins (hypogammaglobulinemia), which are important for fighting infections
• blood test results showing low levels of calcium, sodium, magnesium, potassium, phosphate, or albumin, which can cause fatigue, weakness, or muscle cramps or irregular heartbeats
• blood test results showing high levels of liver enzymes (abnormal liver function tests) or high levels of a protein (C-reactive protein) in the blood, which can be a sign of inflammation.

Common: may affect up to 1 in 10 people

• severe inflammation due to the activation of the immune system, which can cause serious damage to the body
• muscle pain
• abnormal or uncoordinated movements
• irregular heartbeats
• fluid in the lungs
• low oxygen levels in the blood, which can cause difficulty breathing, confusion, or sleepiness.

Rare: may affect up to 1 in 1000 people

• a new type of cancer that starts from a type of white blood cell called T lymphocytes (secondary T-cell neoplasia).

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 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. Storage of Abecma

This information is intended only for healthcare professionals.

Do not use this medicine after the expiry date which is stated on the carton and infusion bag after “EXP”.

Store and transport frozen in the vapor phase of liquid nitrogen (≤−130 °C). Do not thaw the medicine until it is ready to be used. Do not re-freeze.

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

6. Container Content and Additional Information

Composition of Abecma

• The active substance is idecabtagene vicleucel. Each Abecma infusion bag contains a cell dispersion of idecabtagene vicleucel at a concentration dependent on the batch of autologous T lymphocytes genetically modified to express a chimeric receptor for the anti-BCMA antigen (viable T-CAR positive cells). One or more infusion bags contain a total of 260 to 500 × 10^6 viable T-CAR positive cells.
• The other components (excipients) are CryoStor CS10, sodium chloride, sodium gluconate, sodium acetate trihydrate, potassium chloride, magnesium chloride, and water for injectable preparations. See section 2, "Abecma contains sodium, potassium, and DMSO".

This medicinal product contains genetically modified human blood cells.

Appearance and Container Content of the Product

Abecma is a colorless cell dispersion for infusion, supplied in one or more infusion bags individually packaged in a metal cassette. Each bag contains between 10 ml and 100 ml of cell dispersion.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

BMS Netherlands Operations B.V.

Francois Aragostraat 2

2342 DK Oegstgeest

Netherlands

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

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This information is intended for healthcare professionals only:

It is important to read the entire content of this procedure before administering Abecma.

Precautions to be taken before handling or administering the medicinal product

• Abecma should be transported within the facility in closed, break-resistant, and leak-proof containers.
• This medicinal product contains human blood cells. Healthcare professionals handling Abecma should take appropriate precautions (wear gloves and eye protection) to avoid the possible transmission of infectious diseases.

Pre-treatment preparation

• Prior to infusion of Abecma, it should be confirmed that the patient's identity matches the patient identifiers on the cassette(s), infusion bag(s), and Abecma Release for Infusion Certificate (RfIC).
• The Abecma infusion bag should not be removed from the cassette if the patient-specific label information does not match the identity of the patient to be treated. In case of discrepancies between labels and patient identifiers, the company should be contacted immediately.
• If more than one infusion bag is received for treatment, each bag should be thawed one at a time. The thawing time of Abecma should be coordinated with infusion. The start time of infusion should be confirmed in advance and adjusted taking into account thawing so that Abecma is available for infusion when the patient is ready.

Thawing

• Remove the Abecma infusion bag from the cassette and inspect for any loss of container integrity, such as breaks or cracks, prior to thawing. If the infusion bag appears to be damaged or leaking, it should not be infused and should be discarded in accordance with local guidelines for handling human biological materials.
• Place the infusion bag inside a second sterile bag.
• Thaw Abecma at approximately 37 °C using an authorized thawing device or a water bath until no visible ice is present in the infusion bag. Gently mix the contents of the bag to disperse visible cell clumps. Small cell clumps are normal in Abecma. Do not wash, invert, or resuspend Abecma in a new medium prior to infusion.
• The Abecma infusion bag is wrapped in a transparent plastic overwrap that is folded towards the back of the bag. Carefully remove the infusion bag from the overwrap by opening the plastic overwrap at the back to extract it. Pull the bag to remove it completely from the overwrap.

Administration

• DO NOT use a leucodepletion filter.
• The intravenous infusion of Abecma should only be administered by a healthcare professional with experience in treating immunocompromised patients and prepared to manage anaphylaxis.
• Ensure that tocilizumab and emergency equipment are available prior to infusion and during the recovery period. In the exceptional case where tocilizumab is not available due to a shortage listed in the European Medicines Agency's shortage catalog, ensure that adequate alternative measures are available at the center, instead of tocilizumab, to treat CRS.
• A central venous access may be used for the infusion of Abecma and is recommended in patients with poor peripheral access.
• Prior to administration, it should be confirmed that the patient's identification data match the information on the Abecma infusion bag and accompanying documentation. The total number of infusion bags to be administered should also be confirmed by checking the patient-specific information on the Release for Infusion Certificate (RfIC).
• Prime the infusion line with a 9 mg/ml (0.9%) sodium chloride injectable solution before infusion. An in-line filter (a non-leucodepletion filter with a pore size range of 170 to 260 μm) should be used for thawed medicinal products.
• Infuse Abecma within 1 hour from the start of thawing at the maximum tolerated rate by gravity flow.
• Once the entire contents of the infusion bag have been infused, the line, including the in-line filter, should be flushed with a 9 mg/ml (0.9%) sodium chloride injectable solution at the same infusion rate to ensure that as many cells as possible are infused to the patient.
• All other infusion bags for the identified patient should be administered following the same procedure.

Measures to be taken in case of accidental exposure

• In case of accidental exposure, local guidelines for handling human biological materials should be followed. Work surfaces and materials that may have come into contact with Abecma should be decontaminated with an appropriate disinfectant.

Precautions to be taken for the disposal of the medicinal product

• Unused medicinal product and all materials that have come into contact with Abecma (solid and liquid waste) should be handled and disposed of as potentially infectious human biological waste in accordance with local guidelines.