Prospect: information for the patient

CARVYKTI 3,2 × 106– 1,0 × 108células, dispersión para perfusión

ciltacabtagén autoleucel (viable CAR+ T cells)

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.
• Your doctor or nurse will give you a patient information card that contains important safety information about the treatment with CARVYKTI. Read it carefully and follow the instructions.
• Carry the patient information card with you at all times and show it to any doctor or nurse who treats you or if you visit the hospital.

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

How CARVYKTI works

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

You should not receive CARVYKTI

• if you are allergic to any of the components of this medication (listed in section 6).
• if you are allergic to any of the components of the medications that will be administered to reduce the number of white blood cells in the blood (lymphodepletion treatment) before receiving CARVYKTI (also see section 3, How CARVYKTI is administered).

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

Warnings and precautions

Inform your doctor before receiving CARVYKTI if you have:

• current or past nervous system problems, such as seizures, strokes, new or worsening memory loss.
• any lung, heart, or blood pressure problems.
• liver or kidney problems.
• signs or symptoms of graft-versus-host disease. This disease occurs when the transplanted cells attack your body, causing symptoms such as skin rash, nausea, vomiting, diarrhea, 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: the infection will be treated before CARVYKTI administration
• check if your cancer is worsening
• check if you have hepatitis B, hepatitis C, or HIV infection
• check if you have been vaccinated in the past 6 weeks or plan to be vaccinated in the coming months.

After treatment with CARVYKTI, your doctor will:

• periodically monitor your blood, 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 bruises or bleeding.

Be aware of possible severe side effects

There are severe side effects that you must immediately report to your doctor or nurse and may require immediate medical attention. See section 4, "Severe side effects".

Children and adolescents

CARVYKTI should not be used in children and adolescents under 18 years old, as the medication has not been studied in this age group and its safety and efficacy are unknown.

Other medications and CARVYKTI

Before receiving CARVYKTI, inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication, especially:

• immunosuppressive medications such as corticosteroids.

These medications may interfere with the effect of CARVYKTI.

Vaccines and CARVYKTI

You should not be vaccinated with certain live vaccines:

• in the 6 weeks before receiving the short cycle of chemotherapy (lymphodepletion 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, or think you may be pregnant, consult your doctor before receiving this medication.

• This is because the effects of CARVYKTI on pregnant or breastfeeding women are unknown.
• CARVYKTI may harm the fetus or infant.

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

Before starting treatment, a pregnancy test should be performed. CARVYKTI should only be administered if the results indicate that you are not pregnant.

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

Driving and using tools or machines

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

• fatigue
• balance and coordination problems
• confusion, weakness, or dizziness.

Do not drive or use tools or machines at least 8 weeks after receiving CARVYKTI or if those symptoms return.

CARVYKTI contains dimethyl sulfoxide (DMSO) and kanamycin

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

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

Production of CARVYKTI from your own blood cells

CARVYKTI is produced from your own white blood cells. To prepare your medication, they will extract blood cells from you.

• Your doctor will extract some of your blood using a catheter (vein) placed in a vein.
• Some of the white blood cells will be separated from the blood; the rest of the blood will be returned to the vein. This process is called “leucaféresis”.
• This process may take 3 to 6 hours and may need to be repeated.
• Your white blood cells will be sent to the production center, where they will be modified to produce CARVYKTI. This process takes approximately 4 weeks.
• While CARVYKTI is being produced, you may receive other medications to treat multiple myeloma. This is done to prevent it from getting worse.

Medications administered before CARVYKTI treatment

A few days before, you will be administered a treatment called “lymphodepletion” to prepare your body to receive CARVYKTI. This treatment reduces the number of white blood cells in the blood, so that the genetically modified white blood cells of CARVYKTI can grow in number when they are returned to your body.

You may be administered other medications30 to 60 minutes before. These may include:

• Antihistamines in case of an allergic reaction, such as diphenhydramine
• medications for fever such as paracetamol.

Your doctor or nurse will carefully check if CARVYKTI treatment proceeds from your own white blood cells.

How CARVYKTI is administered

CARVYKTI is a treatment that is only done once and will not be administered again.

• Your doctor or nurse will administer CARVYKTI through 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 the necessary precautions to avoid the possibility of transmission of infectious diseases.
• They will also follow local guidelines to clean or dispose of any material that has come into contact with CARVYKTI.

After CARVYKTI administration

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

• After receiving CARVYKTI treatment, you must return to the hospital every day for at least 14 days. This is done so that your doctor can check if the treatment is working and treat you if you experience any adverse effects. If you experience severe adverse effects, you may need to stay in the hospital until they are controlled and you can be safely discharged.
• If you miss an appointment, please contact your doctor or qualified center as soon as possible to reschedule.

• To monitor your health status and better understand the long-term effects of CARVYKTI, you will be asked to register for at least 15 years.
• The presence of CARVYKTI in the blood may cause some commercial HIV tests to give a false positive result, although you may be HIV negative.
• Do not donate blood, organs, tissues, or cells for transplants after CARVYKTI treatment.

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

CARVYKTI may cause side effects that could be severe or even fatal.

Severe side effects

Seek immediate medical attention if you experience any of the following severe side effects that could be severe or even fatal.

• A severe immune reaction called “cytokine release syndrome (CRS)” some of whose signs 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 cause dizziness or disorientation.

• Effects on the nervous system, symptoms that can occur days or weeks after receiving the infusion and that may initially be subtle. Some of these symptoms may be signs of a severe 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,
• changes in personality, which may include being less talkative, feeling disinterested in activities, and reduced facial expression.

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

If you observe any of the above side effects, seek immediate medical attention.

Other side effects

The following are other side effects. If you experience any of these side effects, report them to your doctor or nurse.

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

• nasal infection, sinus infection, or throat infection (cold)
• bacterial infection
• cough, shortness of breath
• headache
• pain, including muscle and joint pain
• stomach pain
• swelling caused by fluid accumulation in the body
• intense fatigue
• nausea (feeling sick), reduced appetite, constipation, vomiting, diarrhea
• problems with movement, including muscle spasms, muscle tension
• nerve damage that can cause tingling, numbness, pain, or loss of sensation
• low levels of certain antibodies called immunoglobulins in the blood, which can cause infections
• abnormal blood test results indicating:

• a reduced number of white blood cells (including neutrophils and lymphocytes), which may occur 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, which makes it difficult to form clots
• high levels of a protein called “ferritin” in the blood
• high levels in the blood of certain enzymes called “alkaline phosphatase”, “lactate dehydrogenase”, “gamma-glutamyltransferase”, and “transaminases”

• low oxygen levels in the blood, which causes difficulty breathing, cough, headache, and confusion
• high blood pressure

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

• abnormal heart rhythm
• bleeding, which may be severe, called “hemorrhage”
• kidney failure
• lung infection (pneumonia)
• viral infection
• fungal infection
• severe infection throughout the body (sepsis)
• severe immune reaction affecting blood cells: may cause an enlarged liver and spleen, which is 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
• high levels of “bilirubin” in the blood
• blood clot
• skin rash
• high levels of a protein called “C-reactive protein” in the blood, which may indicate an infection or inflammation
• severe confusion
• a type of infection caused by the herpes virus, called “cytomegalovirus”

If you experience any of these side effects, report them to your doctor or nurse. Do not attempt to treat your symptoms with other medications on your own.

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is not listed in this leaflet. You can also report them directly through the national notification system included in Appendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

This information is intended only for physicians.

Do not use this medication after the expiration date that appears on the label of the container and on the infusion bag after “CAD”.

Store frozen in liquid nitrogen vapor phase (≤ -120 °C) until it is necessary to thaw it for use.

Do not re-freeze.

Composition of CARVYKTI

The active ingredient is ciltacabtagene autoleucel.

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

Each infusion bag contains 30 ml or 70 ml of infusion dispersion.

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

This medicine contains genetically modified human cells.

Appearance of the product and contents of the pack

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

Marketing authorisation holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Responsible person

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden

Netherlands

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

Last update of the summary of product characteristics: MM/AAAA.

This medicinal product has been authorisedwith a "conditional approval".

This type of approval means that more information about this medicinal product is expected to be obtained.

The European Medicines Agency will review the new information about this medicinal product at least once a year and this summary of product characteristics will be updated as necessary.

Other sources of information

Detailed information about this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu

This information is intended solely for healthcare professionals:

CARVYKTI should not be irradiated, as irradiation could inactivate the medicinal product.

Precautions to be taken before handling or administering the medicinal product

CARVYKTI should be transported within the centre in closed, breakage-proof and leak-proof containers.

This medicinal product contains human blood cells. Healthcare professionals handling CARVYKTI should take the necessary precautions (wear gloves, protective clothing and eye protection) to avoid the possible transmission of infectious diseases.

CARVYKTI should remain at all times at ≤ -120 ºC, until the moment of thawing the contents of the infusion bag.

Preparation before administration

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

• Before preparing CARVYKTI, the patient's identity should be confirmed by comparing it with the patient's identifiers on the cryogenic container of CARVYKTI and the batch information leaflet. The infusion bag of CARVYKTI should not be removed from the cryogenic container if the specific patient information on the label does not match the intended patient.
• Once the patient's identity has been confirmed, the infusion bag is removed from the cryogenic container.
• The infusion bag should be inspected to check that there is no damage to the integrity of the packaging, such as cracks or breaks, both before and after thawing. Do not administer the product if the bag is damaged and contactJanssen-Cilag International NV.

Thawing

• Before thawing, the infusion bag should be placed inside a plastic bag with a hermetic closure.
• CARVYKTI should 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 of thawing to its completion should not exceed 15 minutes.
• The infusion bag should be removed from the plastic bag with a hermetic closure and dried with a cloth. The contents of the infusion bag should be gently mixed to disperse the aggregated cells. If cell aggregates are observed, continue to mix the contents of the infusion bag gently. Small cell aggregates should be dispersed manually and gently. CARVYKTI should not be pre-filtered in a different container, washed, centrifuged, and/or re-suspended in new media before infusion.
• Once thawed, the medicinal product should not be re-frozen or refrigerated.

Administration

• CARVYKTI is exclusively for single autologous use.
• Before infusion and during the recovery period, ensure that tocilizumab and an emergency kit are available. In the exceptional case where tocilizumab is not available due to a shortage listed on the European Medicines Agency's shortage list, ensure that the centre has adequate alternative measures for the treatment of SLC in place instead of tocilizumab.
• Confirm the patient's identity with the patient's identifiers on the infusion bag of CARVYKTI and the batch information leaflet. Do not infuse CARVYKTI if the information on the specific patient label does not match the intended patient.
• Once thawed, the entire contents of the infusion bag of CARVYKTI should be administered via intravenous infusion within 2.5 hours at room temperature (20 ºC to 25 ºC), using infusion equipment with an in-line filter. The infusion usually lasts less than 60 minutes.
• Do not use a leucodepletion filter.
• Mix the contents of the infusion bag gently during the infusion of CARVYKTI to disperse the aggregated cells.
• Once the contents of the infusion bag have been infused, the administration route, including the in-line filter, should be flushed with a 9 mg/ml (0.9 %) sodium chloride injection solution to ensure that the entire medicinal product is administered.

Precautions to be taken for the disposal of the medicinal product

The handling and disposal of unused medicinal product and all materials that have come into contact with CARVYKTI (solid and liquid waste) should be carried out as if they were potentially infectious materials and in accordance with local regulations on the handling of human origin materials.

Measures to be taken in case of accidental exposure

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