Carvykti

Patient Information Leaflet

CARVYKTI 3.2 × 10⁶ - 1 × 10⁸ cells for infusion dispersion

ciltacabtagene autoleucel (chimeric antigen receptor [CAR]-expressing viable T cells)

This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you are given this medicine, as 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 get any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.
• Your doctor or nurse will give you a patient alert card containing important safety information about treatment with CARVYKTI. Please read it carefully and follow the instructions provided.
• Always carry your patient alert card and show it to any doctor or nurse treating you, or if you go to hospital.

Contents of this leaflet

1. What CARVYKTI is and what it is used for
2. What you need to know before you are given 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 cell therapy”. It is specially made for you using your own white blood cells, called T cells.
• CARVYKTI is used to treat adult patients with a bone marrow cancer called multiple myeloma. It is given when at least one other treatment has not worked.

How CARVYKTI works

• The white blood cells taken from your blood have been modified in the laboratory by adding a gene that causes them to produce a protein called a chimeric antigen receptor (CAR).
• The CAR can bind to a specific surface protein on myeloma cells, enabling the white blood cells to recognize and attack the myeloma cells.

2. What you should know before being given CARVYKTI

You must not be given CARVYKTI

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

If you think you might be allergic, consult your doctor.
Warnings and precautions
Patients treated with CARVYKTI may develop new types of cancer. Cases have been reported of patients who, after treatment with CARVYKTI and similar medicines, developed a cancer originating from blood cells. Contact your doctor if you experience new swelling of the glands (lymph nodes) or skin changes, such as new lumps or rashes.
Before you are given CARVYKTI, you must inform your doctor if:

• you have or have had problems with the nervous system, such as seizures, stroke, recent memory loss, or worsening memory loss;
• you have any problems with your lungs, heart, or blood pressure (low or high);
• you have problems with your liver or kidneys;
• you have signs or symptoms of graft-versus-host disease. This occurs when transplanted cells attack the body, causing symptoms such as rash, nausea, vomiting, diarrhoea, and blood in the stool.

If you fall into any of the above conditions (or if you have any doubts), consult your doctor before
being given CARVYKTI.
Tests and monitoring
Before administering CARVYKTI, your doctor will:

• check your blood cell levels;
• perform an evaluation of your lungs, heart, and blood pressure;
• look for signs of infection; any infection present will be treated before you are given CARVYKTI;
• assess whether your tumour is worsening;
• test for hepatitis B, hepatitis C, or HIV infection;
• check whether you have received any vaccination within the past 6 weeks or whether you plan to receive one in the coming months.

After treatment with CARVYKTI, your doctor will:

• regularly monitor your blood counts, as the number of blood cells and other blood components may decrease. Inform your doctor immediately if you develop fever, chills, or any signs or symptoms of infection, or if you feel tired, or have bruising or bleeding.

Be aware of serious side effects
Serious side effects may occur, which you must report immediately to your doctor or nurse, as they may require immediate medical treatment. See section 4 below, “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 not known whether it is safe and effective.
Other medicines and CARVYKTI
Before you are given CARVYKTI, inform your doctor or nurse if you have recently taken or might take any other medicine.
In particular, inform your doctor or nurse if you are taking:

• medicines that weaken the immune system, such as corticosteroids. These medicines may interfere with the effect of CARVYKTI.

Vaccines and CARVYKTI
You must not receive certain vaccines known as live vaccines:

• within 6 weeks before undergoing a short course of chemotherapy (called lymphodepleting chemotherapy) to prepare your body to receive CARVYKTI cells;
• after treatment with CARVYKTI while your immune system is recovering. If you need any vaccinations, discuss this with your doctor.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.

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

If you are pregnant or think you might be pregnant after treatment with CARVYKTI, consult your doctor immediately.
You will need to have a pregnancy test before starting treatment. CARVYKTI must only be administered if test results confirm you are not pregnant.
If you have received CARVYKTI, you should discuss with your doctor your intention to become pregnant in the future.
Driving and using machines
CARVYKTI may severely impair your ability to drive or use tools or machinery, due to side effects that may:

• cause tiredness;
• cause problems with balance and coordination;
• cause confusion, weakness, or dizziness. Do not drive or use tools or machinery for at least 8 weeks after receiving CARVYKTI, and 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), either of which may occasionally cause allergic reactions. Your doctor will monitor you for any signs of a possible allergic reaction.

3. How CARVYKTI is administered

CARVYKTI will always be administered to you by a healthcare professional at a qualified treatment centre.

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

• Your doctor will draw your blood using a catheter (tube) inserted into a vein.
• White blood cells will be separated from the blood, while the remaining blood will be returned to the vein. This procedure is called "leukapheresis".
• The procedure may take from 3 to 6 hours and may need to be repeated.
• Your white blood cells will be sent to a manufacturing centre where they will be genetically modified to produce CARVYKTI. This process will take approximately 4 weeks.
• While waiting for CARVYKTI to be manufactured, you may receive other medications to treat multiple myeloma and prevent disease progression.

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 the blood so that the number of genetically modified white blood cells present in CARVYKTI can increase once they are infused back into your body.
30 to 60 minutes before: you may be given other medications. These may include:

• antihistamines for allergic reactions, such as diphenhydramine
• medications for fever, such as paracetamol.
  Your doctor or nurse will carefully verify that the CARVYKTI treatment being administered to you was produced from your own white blood cells.

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

• Your doctor or nurse will administer CARVYKTI to you via intravenous infusion. This procedure, known as "intravenous infusion", usually takes less than 60 minutes. CARVYKTI consists of your own white blood cells that have been genetically modified.
• The healthcare professional handling CARVYKTI will take appropriate precautions to prevent the potential transmission of infectious diseases.
• They will also follow local guidelines for cleaning or disposing of any materials that have come into contact with CARVYKTI.

After administration of CARVYKTI

• Plan to remain near the hospital where you received treatment for at least 4 weeks after receiving CARVYKTI.
• After receiving CARVYKTI, you will need to return to the hospital daily for at least 14 days. This will allow your doctor to monitor whether the treatment is working and to manage any side effects promptly. If you develop severe side effects, you may need to remain in the hospital until the side effects are under control and it is safe for you to be discharged.
• If you miss an appointment, contact your doctor or qualified treatment centre as soon as possible to reschedule.
• You will be asked to enroll in a monitoring registry for at least 15 years to monitor your health and better understand the long-term effects of CARVYKTI.
• The presence of CARVYKTI in your blood may cause certain commercial HIV tests to give a false positive result, even if you are HIV-negative.
• Do not donate blood, organs, tissues, or cells for transplantation after receiving CARVYKTI.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
CARVYKTI may cause side effects that can be serious or potentially fatal.
Serious side effects
Contact your doctor immediately if you experience any of the following serious side effects, which may be severe and even fatal.

• A severe immune reaction known as "cytokine release syndrome" (CRS), whose signs may include:

Very common (may affect more than 1 in 10 people):
o chills, fever (38 °C or higher),
o rapid heartbeat, difficulty breathing,
o low blood pressure, which may cause dizziness or feeling faint.

• Effects on the nervous system, whose symptoms may occur days or weeks after infusion and may initially be mild. 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):
o feeling confused,
o reduced alertness, disorientation, anxiety, memory loss,
o difficulty speaking or slurred speech,
o slowed movements, changes in handwriting
Common (may affect up to 1 in 10 people):
o loss of coordination affecting movement and balance,
o difficulty reading, writing, and understanding words,
o changes in personality, which may include reduced talkativeness,
lack 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 side effects, seek immediate medical help.
Other side effects
The following are other side effects. Inform your doctor or nurse if you experience any of these.
Very common (may affect more than 1 in 10 people):

• infection of the nose, sinuses, or throat (common cold)
• bacterial infection
• cough, shortness of breath
• pneumonia (lung infection)
• viral infection
• headache
• sleep disturbances
• pain, including muscle and joint pain
• swelling due to fluid buildup in the body
• feeling extremely tired
• nausea (feeling unwell), loss of appetite, constipation, vomiting, diarrhea
• movement problems including muscle spasms, muscle stiffness
• nerve damage that may cause tingling, numbness, pain, or loss of sensitivity to pain
• low levels of antibodies called immunoglobulins in the blood, which may lead to infections
• low levels of oxygen in the blood causing shortness of breath, cough, headache, and confusion
• increased blood pressure
• bleeding, even severe, known as “haemorrhage”
• abnormal blood test results indicating:
• low white blood cell count (including neutrophils and lymphocytes)
• low levels of “platelets” (cells involved in blood clotting) and red blood cells
• low levels of calcium, sodium, potassium, magnesium, phosphate in the blood
• low levels of “albumin”, a type of protein in the blood
• blood clotting problems
• increased levels of a protein called “ferritin” in the blood
• increased levels of enzymes in the blood called “gamma-glutamyl transferase” and “transaminases”

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

• low white blood cell count (neutrophils), which may occur with infection and fever
• gastroenteritis (inflamed stomach and intestines)
• stomach pain
• urinary tract infection
• fungal infection
• increased number of a type of white blood cells (lymphocytes)
• severe whole-body infection (sepsis)
• kidney failure
• abnormal heartbeat
• severe immune reaction involving blood cells: may cause enlargement of the liver and spleen, called “hemophagocytic lymphohistiocytosis”
• a serious condition in which fluid leaks from blood vessels into body tissues, called “capillary leak syndrome”
• increased levels of enzymes in the blood called “alkaline phosphatase”
• muscle tremors
• mild muscle weakness caused by nerve damage
• severe confusion
• facial numbness, difficulty moving facial and eye muscles
• high levels of “bilirubin” in the blood
• blood clots
• rash
• increased level of a protein in the blood called “C-reactive protein”, which may indicate infection or inflammation
• a new type of cancer originating in blood cells, including bone marrow cells

Uncommon (may affect up to 1 in 100 people):

• tingling, numbness, and pain in hands and feet, difficulty walking, weakness in legs and/or arms, and difficulty breathing
• a new type of cancer originating in a type of white blood cells called T cells (malignant secondary neoplasm of T-cell origin)

Inform your doctor or nurse if you experience any of the side effects listed above.
Do not attempt to treat symptoms by taking other medicines on your own.
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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store CARVYKTI

The following information is intended for physicians only.
Do not use this medicinal product after the expiry date stated on the outer carton and on the infusion bag after “Exp.”.
Store frozen in liquid nitrogen vapour (≤-120 °C) until thawing for use.
Do not refreeze.

6. Package contents and other information

What CARVYKTI contains
The active substance is ciltacabtagene autoleucel.
Each CARVYKTI infusion bag contains a cellular dispersion of ciltacabtagene autoleucel consisting of 3.2 × 10⁶ - 1 × 10⁸ viable CAR-positive T cells suspended in a cryopreservation solution.
An infusion bag contains either 30 mL or 70 mL of infusion dispersion.
The other excipients 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.

Description of the appearance of CARVYKTI and contents of the pack
CARVYKTI is a cellular dispersion for infusion, ranging from colourless to white, with possible white, yellow or pink tinges, 30 mL or 70 mL in volume, supplied in a 50 mL or 250 mL infusion bag, individually packaged in an aluminium cryogenic container.

Marketing Authorization Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Technologiepark-Zwijnaarde 73
9052, Ghent
Belgium
Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

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

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB “JOHNSON & JOHNSON”
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark
Janssen-Cilag A/S Malta
Tlf: +45 4594 8282 AM MANGION LTD
[email protected] Tel: +356 2397 6000

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: 0800 086 9247 / +49 2137 955 6955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB “JOHNSON & JOHNSON” Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Janssen-Cilag Pharma GmbH
Α.Ε.Β.Ε. Tel: +43 1 610 300
Tηλ: +30 210 80 90 000

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

Portugal
France Janssen-Cilag Farmacêutica, Lda.
Janssen-Cilag Tel: +351 214 368 600
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
[email protected]

România
Hrvatska Johnson & Johnson România SRL
Johnson & Johnson S.E. d.o.o. Tel: +40 21 207 1800
Tel: +385 1 6610 700
[email protected]

Slovenija
Ireland Johnson & Johnson d.o.o.
Janssen Sciences Ireland UC Tel: +386 1 401 18 00
Tel: 1 800 709 122 [email protected]
[email protected]

Slovenská republika
Ísland Johnson & Johnson, s.r.o.
Janssen-Cilag AB Tel: +421 232 408 400
c/o Vistor hf.
Sími: +354 535 7000
[email protected]

Suomi/Finland
Italia Janssen-Cilag Oy
Janssen-Cilag SpA Puh/Tel: +358 207 531 300
Tel: 800.688.777 / +39 02 2510 1 [email protected]
[email protected]

Sverige
Κύπρος Janssen-Cilag AB
Βαρνάβας Χατζηπαναγής Λτδ Tfn: +46 8 626 50 00
Τηλ: +357 22 207 700 [email protected]

Latvija
UAB “JOHNSON & JOHNSON” filiāle Latvijā
Tel: +371 678 93561
[email protected]

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 exclusively for healthcare professionals:

CARVYKTI must not be irradiated, as radiation may cause inactivation of the medicinal product.
Precautions to be taken before handling or administration of the medicinal product
CARVYKTI must be transported within the facility in closed, break-resistant, and leak-proof containers.
This medicinal product contains human blood cells. Healthcare professionals handling CARVYKTI must take appropriate precautions (wearing gloves, protective clothing, and eye protection) to avoid potential transmission of infectious diseases.
CARVYKTI must always be maintained at ≤ -120 °C until the bag contents are thawed 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 should be adjusted so that CARVYKTI is available for infusion when the patient is ready.
Once thawed, the medicinal product must be administered immediately, and the infusion must be completed within 2.5 hours.

• Before preparing CARVYKTI, verify that the patient's identity matches the identification details 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 label information does not match the patient to be treated.
• After confirming patient identification, the CARVYKTI infusion bag must be removed from the cryogenic container.
• The infusion bag must be inspected before and after thawing for any compromise in container integrity, such as breaks or cracks. Do not administer if the bag is compromised and contact Janssen-Cilag International NV.

Thawing

• Prior to thawing, the infusion bag must be placed inside a resealable plastic bag.
• CARVYKTI must be thawed at 37 °C ± 2 °C using a water bath or a dry thawing device until no visible ice remains in the infusion bag. The total time from the beginning to the end of thawing must not exceed 15 minutes.
• The infusion bag must be removed from the resealable plastic bag and dried. The contents of the infusion bag should be gently mixed to disperse any clumps of cellular material. If visible cellular clumps remain, continue gently mixing the bag contents. Disperse small clumps of cellular material by gentle manual mixing. CARVYKTI must not be pre-filtered into another container, washed, inverted, or resuspended in a new medium prior to infusion.
• Once thawed, the medicinal product must not be refrozen or refrigerated.

Administration

• CARVYKTI is for single autologous use only.
• Ensure that tocilizumab and emergency equipment are available before infusion and during the recovery period. In the rare event that tocilizumab is unavailable due to a shortage listed in the European Medicines Agency’s list of unavailable medicines, appropriate alternative measures for the treatment of CRS must be available on-site prior to infusion.
• Verify that the patient's identity matches the identification details on the CARVYKTI infusion bag and the batch information sheet. Do not infuse CARVYKTI if the patient-specific label information does not match the patient to be treated.
• Once thawed, the entire contents of the CARVYKTI bag must be administered by intravenous infusion within 2.5 hours at room temperature (20 °C - 25 °C), using an infusion set with an in-line filter. The infusion typically lasts less than 60 minutes.
• DO NOT use a leukocyte depletion filter.
• Gently mix the bag contents during infusion of CARVYKTI to disperse cellular clumps.
• After infusion of the entire bag contents, flush the administration line, including the in-line filter, with 9 mg/mL (0.9%) sodium chloride injection solution to ensure that all of the medicinal product has been administered.

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

Measures to be taken in case of accidental exposure
In the event of accidental exposure, follow local guidelines for handling human-derived materials. Work surfaces and materials that may have come into contact with CARVYKTI must be decontaminated using appropriate disinfectants.