Breyanzi 1.1-70 × 10E6 cells/mL / 1.1-70 × 10E6 cells/mL dispersion for infusion: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Breyanzi 1.1-70 × 10⁶ cells/ml / 1.1-70 × 10⁶ cells/ml infusion dispersion

lisocabtagene maraleucel (viable chimeric antigen receptor [CAR]-positive T cells)

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Section 4 at the end 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, as you may need to read it again.
Your doctor will give you a patient card. Read the card carefully and follow the instructions it contains.
Always show the patient card to your doctor or nurse when you see them, or if you go to a hospital.
If you have any questions, ask your doctor or nurse.
If you experience any side effects, talk to your doctor or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of this leaflet

What Breyanzi is and what it is used for
What you need to know before you are given Breyanzi
How Breyanzi is administered
Possible side effects
How to store Breyanzi
Contents of the pack and other information

1. What Breyanzi is and what it is used for

What Breyanzi is

Breyanzi contains the active substance lisocabtagene maraleucel, a type of treatment known as "genetically modified cellular therapy".

Breyanzi is made from your own white blood cells. This involves taking some of your blood, separating the white blood cells, and sending them to a laboratory so they can be genetically modified to produce Breyanzi.

What Breyanzi is used for

Breyanzi is used to treat adults with a type of blood cancer called lymphoma, which affects the lymphatic tissue and causes white blood cells to grow uncontrollably. Breyanzi is used for:

diffuse large B-cell lymphoma;
high-grade B-cell lymphoma;
primary mediastinal large B-cell lymphoma;
follicular lymphoma;
mantle cell lymphoma.

How Breyanzi works

The cells in Breyanzi have been genetically modified to recognize lymphoma cells present in your body.
When these cells are reintroduced into your bloodstream, they will recognize and attack the lymphoma cells.

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

Do not receive Breyanzi

if you are allergic to any of the components of this medicine (listed in section 6). If you think you may be allergic, consult your doctor
if you cannot receive the treatment called lymphodepleting chemotherapy, which reduces the number of white blood cells in your blood (see also section 3 “How Breyanzi is given”).

Warnings and precautions

Before receiving Breyanzi, you must tell your doctor if

you have lung or heart problems
you have low blood pressure
you have an infection or other inflammatory conditions. Any infection will be treated before you are given Breyanzi
you received a hematopoietic progenitor cell transplant from another person within the last 4 months. The transplanted cells may attack your own body (graft-versus-host disease), causing symptoms such as rash, nausea, vomiting, diarrhea, and blood in the stool
you notice that your cancer symptoms are worsening. These symptoms include fever, feeling weak, night sweats, or sudden weight loss
you have had hepatitis B or C, or human immunodeficiency virus (HIV) infection
you have been vaccinated within the last 6 weeks or are scheduled to receive a vaccine in the coming months. See Live vaccines below for more information.

If any of the above apply to you (or if you are unsure), consult your doctor before receiving Breyanzi.

Patients treated with Breyanzi may develop new types of cancer. Cases have been reported of patients developing cancer originating from a type of white blood cells called T lymphocytes, after treatment with Breyanzi and similar medicines. Consult 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 Breyanzi, your doctor will

examine your lungs, heart, and blood pressure
look for signs of infection (any infection will be treated before Breyanzi is administered)
look for signs of “graft-versus-host disease,” which may occur after a hematopoietic progenitor cell transplant from another person
perform a blood test to check your uric acid levels and determine the number of cancer cells in your blood. This will indicate whether you are at risk of developing a condition called tumor lysis syndrome. You may be given medications to prevent this condition
check whether your cancer is worsening
perform a blood test to detect hepatitis B and C and HIV infection.
After receiving Breyanzi
If you experience certain serious side effects, you must inform your doctor or nurse immediately, as you may require treatment for them. See “serious side effects” in section 4
Your doctor will perform periodic blood tests to monitor your blood counts, as the number of blood cells may decrease
You must remain close to the treatment center where you received Breyanzi for at least 2 weeks. Your doctor may recommend staying closer to the center for a longer period to ensure that post-treatment care meets your individual needs. See sections 3 and 4
You must not donate blood, organs, tissues, or cells for transplantation.

You will be asked to enroll in a registry for at least 15 years to better understand the long-term effects of Breyanzi.

Children and adolescents

Breyanzi must not be given to children and adolescents under 18 years of age.

Other medicines and Breyanzi

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including over-the-counter medicines.

For information about the medicines you will be given before Breyanzi, see section 3.

Medicines that affect the immune system

Before receiving Breyanzi, inform your doctor or nurse if you are taking medicines that weaken the immune system, for example:

corticosteroids.

You should do so because these medicines may reduce the effect of Breyanzi.

Other medicines for treating cancer

Some cancer medicines may reduce the effect of Breyanzi. Your doctor will assess whether you need other cancer treatments.

Live vaccines

You must not receive certain vaccines, particularly live vaccines:

within 6 weeks before receiving the short course of chemotherapy (called lymphodepleting chemotherapy) given to prepare your body for Breyanzi;
during treatment with Breyanzi;
after treatment, while your immune system is recovering.

Consult 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, consult your doctor before receiving this medicine or lymphodepleting chemotherapy. The effects of Breyanzi in pregnant or breastfeeding women are unknown and may be harmful to the unborn baby or infant.

If you are pregnant or think you may be pregnant after treatment with Breyanzi, consult your doctor immediately.
A pregnancy test will be performed before starting treatment. Breyanzi should only be administered if test results indicate you are not pregnant.

Consult your doctor about the need for contraception.

If you have received Breyanzi, consult your doctor about pregnancy.

Driving and use of machines

Do not drive, operate machinery, or participate in activities requiring alertness for at least 4 weeks after treatment. Breyanzi may cause drowsiness, reduce alertness, and cause confusion and seizures (epileptic fits). Depending on your individual needs, your doctor may advise you to wait longer before driving.

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

This medicine contains up to 12.5 mg of sodium (a main component of table/cooking salt) in each vial. This corresponds to 0.6% of the maximum daily recommended sodium intake for an adult. Up to 8 vials of this medicine may be administered per dose, resulting in a total of 100 mg of sodium, or 5% of the maximum daily recommended sodium intake for an adult.

This medicine contains up to 0.2 mmol (or 6.5 mg) of potassium per dose. Your doctor will take this potassium content into account if your kidneys are not functioning properly or if you are on a low-potassium diet.

This medicine also contains DMSO, which may cause severe hypersensitivity reactions.

3. How Breyanzi is administered

Patient card

Your doctor will give you a patient card. Read the card carefully and follow the instructions it contains.
Always show the patient card to your doctor or nurse when you see them, or if you go to a hospital.

Donation of blood to manufacture Breyanzi from your white blood cells

Breyanzi is manufactured from your white blood cells.

Your doctor will draw your blood through an intravenous line (catheter) placed into a vein. Some of your white blood cells will be separated from your blood. The rest of the blood will be returned to your body. This procedure is called "leukapheresis" and may take from 3 to 6 hours. It may be necessary to repeat the procedure.
Your white blood cells will then be sent for the manufacturing of Breyanzi.

Other medicines you will receive before Breyanzi

A few days before receiving Breyanzi, you will be given a short course of chemotherapy. The purpose of this is to eliminate your white blood cells.
Shortly before receiving Breyanzi, you will be given paracetamol and an antihistamine medicine. The purpose of these is to reduce the risk of infusion reactions and fever.

How Breyanzi is administered

Your doctor will verify that Breyanzi has been prepared using your own blood by checking that the patient identification information on the medicine labels matches your details.
Breyanzi is administered by intravenous infusion (drip) into a vein through an intravenous line.
You will receive infusions of CD8-positive cells, followed immediately by infusions of CD4-positive cells. The infusion time may vary, but will normally be less than 15 minutes for each of the two cell types.

After administration of Breyanzi

You must remain close to the treatment center where you received Breyanzi (for at least 2 weeks).
During the first week after treatment, you will need to return to the treatment center 2 to 3 times so your doctor can monitor whether the treatment is working and assist you with any possible side effects. See sections 2 and 4.

If you miss an appointment

Call your doctor or treatment center as soon as possible to reschedule your appointment.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Serious adverse effects

Tell your doctor immediately if you experience any of the following adverse effects after treatment with Breyanzi:

fever, chills or shaking chills, feeling tired, rapid or irregular heartbeat, dizziness, and shortness of breath, which may be signs of a serious condition called "cytokine release syndrome"
confusion, decreased alertness (reduced consciousness), difficulty speaking or slurred speech, tremors, feeling anxious, dizziness, and headache, which may be symptoms of a condition called immune effector cell-associated neurotoxicity syndrome (ICANS) or signs of nervous system problems
feeling hot, fever, chills, or rigors, which may be signs of infection.

Infections may be due to:

low levels of white blood cells, which help fight infections, or
low levels of antibodies called "immunoglobulins."
blurred vision, loss of vision, or double vision, difficulty speaking, weakness or clumsiness in one arm or leg, a change in the way of walking or balance problems, personality changes, disturbances in thinking, memory, and orientation that may lead to confusion. All of these may be symptoms of a serious and potentially life-threatening brain condition known as progressive multifocal leukoencephalopathy (PML). These symptoms may begin several months after completion of treatment and usually develop slowly and gradually over weeks or months. It is important that your family members or caregivers are also aware of these symptoms, as they may notice signs you are not aware of.
feeling very tired, weakness, or shortness of breath, which may be signs of low red blood cell levels (anemia)
bleeding or bruising more easily, which may be signs of low levels of blood cells called platelets.

Tell your doctor immediately if you experience any of the above adverse effects after receiving Breyanzi, as you may need urgent medical treatment.

Other possible adverse effects

Very common: may affect more than 1 in 10 people

difficulty sleeping
low blood pressure, including signs such as dizziness, fainting, or visual disturbances
cough
nausea or vomiting
diarrhea or constipation
stomach pain
swelling of the ankles, arms, legs, and face
skin rash

Common: may affect up to 1 in 10 people

problems with balance or walking
high blood pressure, which may include signs such as severe headache, sweating, or difficulty sleeping
changes in vision
changes in taste
numbness and tingling in the feet or hands
blood clots or problems with blood clotting
bleeding in the intestine
reduced urine output
infusion reactions, such as feeling dizzy, fever, and shortness of breath
low levels of phosphates in the blood
low levels of oxygen in the blood

Uncommon: may affect up to 1 in 100 people

a new type of cancer starting in a type of white blood cells called T lymphocytes (secondary T-cell neoplasia)
rapid breakdown of cancer cells, leading to the release of toxic waste products into the bloodstream: one sign may be dark-colored urine with symptoms of nausea or stomach pain on one side
serious inflammatory condition: symptoms may include fever, rash, enlargement of the liver, spleen, and lymph nodes
heart weakness, causing shortness of breath and swelling of the ankles
fluid around the lungs
stroke or mini-stroke
seizures or fits (epileptic attacks)
weakness of the facial muscles, vocal cords, or body weakness
brain swelling

Reporting of adverse effects

If you experience any kind of adverse effect, consult your doctor or nurse, even if they are adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Breyanzi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the cartons and on the vial label following "EXP".

Store frozen in the vapor phase of liquid nitrogen (≤–130 °C).

6. Contents of the pack and other information

Composition of Breyanzi

The active substance is lisocabtagene maraleucel. Each 4.6 ml vial contains a dispersion of viable CD19 CAR-positive T-lymphocytes (CD8-positive cell component or CD4-positive cell component) at a concentration of 1.1 × 10⁶ to 70 × 10⁶ viable CAR-positive T-lymphocytes/ml of each cellular component. Up to 4 vials of each of the CD8-positive or CD4-positive cellular components may be provided, depending on the concentration of the cryopreserved medicinal product.
The other components (excipients) are Cryostor CS10 (containing dimethyl sulfoxide or DMSO), sodium chloride, sodium gluconate, sodium acetate trihydrate, potassium chloride, magnesium chloride, human albumin, N-acetyl-DL-tryptophan, caprylic acid, and water for injections. See section 2, “Breyanzi contains sodium, potassium and dimethyl sulfoxide (DMSO)”.

This medicinal product contains genetically modified human blood cells.

Presentation of the product and contents of the pack

Breyanzi is a cell dispersion for infusion. It is supplied in vials as a slightly opalescent to opalescent dispersion, colourless to yellowish or brownish yellow. Each vial contains 4.6 ml of cell dispersion of either the CD8-positive cell component or the CD4-positive cell component.

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
The Netherlands

BMS Netherlands Operations B.V.
Francois Aragostraat 2
2342 DK Oegstgeest
The Netherlands

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium

N.V. Bristol-Myers Squibb Belgium S.A.

Tel/Tel: + 32 2 352 76 11