Carvykti 3.2 × 10e6 - 1 × 10e8 cells dispersion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

CARVYKTI 3.2 × 10⁶ – 1.0 × 10⁸ cells, infusion dispersion

ciltacabtagene autoleucel (viable CAR+ T cells)

This medicinal product is subject to additional monitoring, which will allow rapid identification of new safety information. You can help by reporting any side effects you may experience. Section 4 includes information on how to report side effects.

Read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.
• Your doctor or nurse will provide you with a patient information card containing important safety information about CARVYKTI treatment. Read it carefully and follow the instructions.
• Carry the patient information card with you at all times and always show it to any doctor or nurse treating you, or if you go to the hospital.

Contents of the package leaflet

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

1. What CARVYKTI is and what it is used for

• CARVYKTI is a type of medicine called a "genetically modified cellular therapy," which has been specially produced for you using your own white blood cells, known as T lymphocytes.
• CARVYKTI is used to treat adult patients with a bone marrow cancer called multiple myeloma. It is given when at least three other types of treatment have not worked.

How CARVYKTI works

• The white blood cells taken from your blood are modified in the laboratory to introduce a gene that enables them to produce a protein called a chimeric antigen receptor (CAR).
• The CAR can bind to a specific protein on the surface of myeloma cells, allowing your white blood cells to recognize and attack the myeloma cells.

2. What you need to know before using CARVYKTI

Do not receive CARVYKTI

• if you are allergic to any of the components of this medicine (listed in section 6).
• if you are allergic to any of the components of the medicines you will be given to reduce the number of white blood cells in your blood (lymphodepleting treatment) before treatment with CARVYKTI (see also section 3, How CARVYKTI is given).

If you think you may be allergic, consult your doctor.

Warnings and precautions

Tell your doctor before receiving CARVYKTI if you have:

• Current or past neurological problems, such as seizures, strokes, new or worsening memory loss.
• Any lung, heart, or blood pressure problems (low or high).
• Liver or kidney problems.
• Signs or symptoms of graft-versus-host disease. This condition occurs when transplanted cells attack your body, causing symptoms such as rash, nausea, vomiting, diarrhoea, and bloody stools.

If you are in any of the above situations (or are unsure), consult your doctor before receiving CARVYKTI.

Tests and examinations

Before receiving CARVYKTI, your doctor will:

• check your blood cell counts
• evaluate your lungs, heart, and blood pressure
• look for signs of infection: any infection will be treated before CARVYKTI is administered
• check whether your cancer is worsening
• test for hepatitis B, hepatitis C, or HIV infection
• check whether you have been vaccinated within the last 6 weeks or plan to be vaccinated in the coming months.

After treatment with CARVYKTI, your doctor will:

• monitor your blood periodically, as the number of blood cells and other blood components may decrease.

Inform your doctor immediately if you have fever, chills, or any signs or symptoms of infection, if you feel tired, or if you have bruising or bleeding.

Be alert for possible serious side effects

There are serious side effects that you must report immediately to your doctor or nurse, which may require immediate medical attention. See section 4, “Serious side effects”.

Children and adolescents

CARVYKTI must not be used in children and adolescents under 18 years of age, as the medicine has not been studied in this age group and it is unknown whether it is safe and effective.

Other medicines and CARVYKTI

Before receiving CARVYKTI, tell your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines, especially:

• medicines that weaken your immune system, such as corticosteroids.

These medicines may interfere with the effect of CARVYKTI.

Vaccines and CARVYKTI

You must not be vaccinated with certain vaccines, known as live vaccines:

• Within the 6 weeks before you are given the short course of chemotherapy (called lymphodepleting chemotherapy) to prepare your body for CARVYKTI cells.
• After treatment with CARVYKTI, while your immune system is recovering.

Consult your doctor if you need to be vaccinated.

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.

• This is because the effects of CARVYKTI in pregnant or breastfeeding women are unknown.
• CARVYKTI may harm the unborn baby or breastfed infant.

If you are pregnant or think you may be pregnant after treatment with CARVYKTI, consult your doctor immediately.

A pregnancy test must be performed before starting treatment. CARVYKTI should only be given if test results show that you are not pregnant.

If you have received treatment with CARVYKTI, discuss any future pregnancy plans with your doctor.

Driving and using machines

CARVYKTI may substantially affect your ability to drive or use tools or machines, as some side effects could cause:

• tiredness
• problems with balance and coordination
• confusion, weakness, or dizziness.

Do not drive or use tools or machines for at least 8 weeks after receiving CARVYKTI, or if these symptoms recur.

CARVYKTI contains dimethyl sulfoxide (DMSO) and kanamycin

This medicine contains DMSO (a substance used to preserve frozen cells) and may contain traces of kanamycin (an aminoglycoside antibiotic), which may occasionally cause allergic reactions. Your doctor will monitor you for signs of a possible allergic reaction.

3. How CARVYKTI is administered

A healthcare professional will always administer CARVYKTI to you at a qualified center.

Manufacturing CARVYKTI from your own blood cells

CARVYKTI is manufactured from your own white blood cells. To prepare your medicine, your blood cells will be collected.

• Your doctor will draw some of your blood through a catheter (line) placed into a vein.
• Some of the white blood cells are separated from the blood; the rest of the blood is returned to the vein. This process is called "leukapheresis".
• This process may take from 3 to 6 hours and may need to be repeated.
• Your white blood cells will be sent to the manufacturing center, where they are genetically modified to produce CARVYKTI. This process takes approximately 4 weeks.
• While CARVYKTI is being manufactured, you may receive other medications to treat multiple myeloma. This is done to prevent your condition from worsening.

Medications administered before treatment with CARVYKTI

A few days before, you will receive a treatment called "lymphodepleting therapy" to prepare your body to receive CARVYKTI. This treatment reduces the number of white blood cells in your blood so that the genetically modified white blood cells in CARVYKTI can multiply once they are returned to your body.

You may also receive other medications 30 to 60 minutes before administration. These may include:

• Antihistamines to prevent allergic reactions, such as diphenhydramine
• Medications for fever, such as paracetamol.

Your doctor or nurse will carefully verify that the CARVYKTI treatment has been manufactured from your own white blood cells.

How CARVYKTI is administered to you

CARVYKTI is a single-dose treatment and will not be administered to you again.

• Your doctor or nurse will give you CARVYKTI as an intravenous infusion. This usually takes less than 60 minutes.

CARVYKTI is the genetically modified version of your white blood cells.

• The healthcare professional handling CARVYKTI will take appropriate precautions to prevent the possible transmission of infectious diseases.
• They will also follow local guidelines for cleaning or disposing of any material that has come into contact with CARVYKTI.

After administration of CARVYKTI

• After receiving CARVYKTI, you must remain near the hospital where you received treatment for at least 4 weeks.

• After receiving CARVYKTI treatment, you will need to return to the hospital every day for at least 14 days. This is to allow your doctor to monitor whether the treatment is working and to manage any adverse effects. If you experience serious adverse effects, you may need to stay in the hospital until they are under control and it is safe for you to be discharged.

• If you miss any appointment, contact your doctor or qualified center as soon as possible to reschedule.

• To monitor your health and better understand the long-term effects of CARVYKTI, you will be asked to enroll in a registry for at least 15 years.

• The presence of CARVYKTI in your blood may cause certain commercial HIV tests to incorrectly return a positive result, even though you may actually be HIV-negative.

• Do not donate blood, organs, tissues, or cells for transplantation after treatment with CARVYKTI.

4. Possible adverse effects

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

CARVYKTI may cause adverse effects that could be serious or even fatal.

Serious adverse effects

Seek immediate medical help if you experience any of the following serious adverse effects, which could be severe and even fatal.

• A severe immune reaction called "cytokine release syndrome (CRS)", some signs of which are:

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

• chills, fever (38 °C or higher),

• rapid heart rate, difficulty breathing,

• low blood pressure, which may make you feel dizzy or lightheaded.

• Effects on the nervous system, symptoms that may occur days or weeks after receiving the infusion and that may initially be subtle. Some of these symptoms may be signs of a serious immune reaction called "immune effector cell-associated neurotoxicity syndrome (ICANS)" or may be signs and symptoms of parkinsonism:

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

• feeling confused,
• reduced alertness, disorientation, anxiety, memory loss,
• difficulty speaking or slurred speech,
• slower movements, changes in handwriting.

Common (may affect up to 1 in 10 people):

• loss of coordination affecting movement and balance,

• difficulty reading, writing, and understanding words,

• personality changes, which may include being less talkative, loss of interest in activities, and reduced facial expression.

• CARVYKTI may increase the risk of potentially fatal infections that can lead to death.

If you notice any of the above adverse effects, seek immediate medical help.

Other adverse effects

The following is a list of other adverse effects. If you experience any of these, inform your doctor or nurse.

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

• nasal, sinus, or throat infection (common cold)

• bacterial infection

• cough, shortness of breath

• headache

• pain, including muscle and joint pain

• stomach pain

• swelling due to fluid accumulation in the body

• feeling of extreme tiredness

• nausea (feeling unwell), reduced appetite, constipation, vomiting, diarrhea

• movement problems, including muscle spasms, muscle tension

• nerve damage that may cause tingling, numbness, pain, or loss of sensation

• low blood levels of certain antibodies called immunoglobulins, which may lead to infections

• abnormal blood test results indicating:

• reduced number of white blood cells (including neutrophils and lymphocytes), which may occur together with infection and fever

• low levels of "platelets" (cells that help blood clotting) and red blood cells

• low levels of calcium, sodium, potassium, magnesium, phosphate in the blood

• low levels of "albumin", a type of blood protein

• low levels of "fibrinogen", a type of blood protein, making it difficult for blood to clot

• increased blood levels of a protein called "ferritin"

• increased blood levels of enzymes called "alkaline phosphatase", "lactate dehydrogenase", "gamma-glutamyl transferase", and "transaminases"

• low oxygen levels in the blood, causing difficulty breathing, cough, headache, and confusion

• increased blood pressure

Common (may affect up to 1 in 10 people):

• abnormal heartbeat
• bleeding, which may be severe, called "hemorrhage"
• kidney failure
• pneumonia (lung infection)
• viral infection
• fungal infection
• severe infection throughout the body (sepsis)
• severe immune reaction affecting blood cells: may cause enlargement of the liver and spleen, called "hemophagocytic lymphohistiocytosis"
• muscle tremor
• difficulty sleeping
• mild muscle weakness caused by nerve damage
• tingling, numbness, and pain in hands and feet, difficulty walking, weakness in leg and/or arm, and difficulty breathing
• facial numbness, difficulty moving facial and eye muscles
• elevated blood levels of "bilirubin"
• blood clot
• skin rash
• increased levels of a protein called "C-reactive protein" in the blood, which may indicate infection or inflammation
• severe confusion
• a type of infection caused by the herpes virus, called "cytomegalovirus"

If you experience any of these adverse effects, inform your doctor or nurse. Do not attempt to treat your symptoms with other medicines on your own.

Reporting of adverse effects

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

5. Storage of CARVYKTI

The following information is intended for physicians only.

Do not use this medicine after the expiry date stated on the label of the container and on the infusion bag after "EXP".

Store frozen in liquid nitrogen in the vapor phase (≤ -120 °C) until thawing is required for use.

Do not refreeze.

6. Contents of the container and other information

Composition of CARVYKTI

The active substance is ciltacabtagene autoleucel.

Each CARVYKTI infusion bag contains a cell dispersion of ciltacabtagene autoleucel containing 3.2 × 106 to 1.0 × 108 viable CAR-positive T cells suspended in a cryopreservation solution.

An infusion bag contains 30 ml or 70 ml of dispersion for infusion.

The other components are a solution (Cryostor CS5) used to preserve frozen cells (see section 2; CARVYKTI contains DMSO and kanamycin).

This medicinal product contains genetically modified human cells.

Presentation of the product and contents of the container

CARVYKTI is a colourless to white cell dispersion for infusion, including shades of white, yellow, and pink, available in 30 ml or 70 ml, supplied in a 50 ml or 250 ml infusion bag, respectively, individually packaged in an aluminium cryogenic container.

Marketing Authorization Holder

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer responsible for production

Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the latest review of this summary: MM/YYYY.

This medicine has been authorised under a "conditional approval".

This type of approval means that further information on this medicine is expected.

The European Medicines Agency will review new information on this medicine at least once a year, and this summary will be updated as necessary.

Other sources of information

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

This information is intended for healthcare professionals only:

CARVYKTI must not be irradiated, as irradiation could inactivate the medicine.

Precautions to be taken before handling or administering the medicine

CARVYKTI must be transported within the facility in closed, break-resistant and leak-proof containers.

This medicine contains human blood cells. Healthcare professionals handling CARVYKTI must take appropriate precautions (wear gloves, protective clothing, and eye protection) to prevent potential transmission of infectious diseases.

CARVYKTI must be stored at all times at ≤ -120 ºC until the time of thawing the bag contents for infusion.

Preparation prior to administration

The timing of thawing and infusion of CARVYKTI must be coordinated; the infusion time should be confirmed in advance, and the start time of thawing adjusted so that CARVYKTI is available for infusion when the patient is ready. Once thawed, the medicine must be administered immediately, and the infusion must be completed within 2.5 hours.

• Prior to preparing CARVYKTI, confirm patient identity by comparing it with the patient identifiers on the CARVYKTI cryogenic container and the batch information sheet. The CARVYKTI infusion bag must not be removed from the cryogenic container if the patient-specific information on the label does not match the intended patient.
• After patient identification has been confirmed, remove the CARVYKTI infusion bag from the cryogenic container.
• The infusion bag must be inspected before and after thawing to ensure there is no damage to the container integrity, such as breaks or cracks. Do not administer the product if the bag is damaged and contact Janssen-Cilag International NV.

Thawing

• Before thawing, place the infusion bag inside a sealed plastic bag.
• CARVYKTI must be thawed at 37 ºC ± 2 ºC using a water bath or a dry thawing device until no ice is visible in the infusion bag. The total time from the start to the end of thawing must not exceed 15 minutes.
• Remove the infusion bag from the sealed plastic bag and dry it with a cloth. Gently mix the bag contents to disperse any clumped cellular material. If cell clumping is observed, continue gently mixing the bag contents. Small clumps of cellular material should be manually and gently dispersed. CARVYKTI must not be pre-filtered into a different container, washed, centrifuged, and/or resuspended in new media prior to infusion.
• Once thawed, the medicine must not be refrozen or refrigerated.

Administration

• CARVYKTI is intended for single autologous use only.
• Prior to infusion and during the recovery period, ensure that tocilizumab and emergency equipment are available. In the exceptional case where tocilizumab is unavailable due to a shortage listed on the European Medicines Agency's shortage list, ensure that the facility has appropriate alternative measures in place for the treatment of CRS instead of tocilizumab.
• Confirm patient identity using the patient identifiers on the CARVYKTI infusion bag and the batch information sheet. Do not infuse CARVYKTI if the patient-specific label information does not match the intended patient.
• Once thawed, the entire contents of the CARVYKTI bag must be administered as an intravenous infusion within 2.5 hours at room temperature (20 ºC to 25 ºC), using infusion equipment with an in-line filter. The infusion typically lasts less than 60 minutes.
• DO NOT use a leucodepletion filter.
• Gently mix the bag contents during the CARVYKTI infusion to disperse any clumped cells.
• After the entire product has been infused, flush the administration line, including the in-line filter, with 9 mg/ml (0.9 %) sodium chloride solution for injection to ensure complete delivery of the medicine.

Precautions for disposal of the medicine

Handling and disposal of unused medicine and all materials that have been in contact with CARVYKTI (solid and liquid waste) must be carried out as if they were potentially infectious waste, in accordance with local regulations for handling human-origin materials.

Measures to be taken in case of accidental exposure

In the event of accidental exposure, follow local regulations for handling human-origin materials. Work surfaces and materials that may have come into contact with CARVYKTI must be decontaminated using an appropriate disinfectant.