ARE YOU ELIGIBLE FOR CARVYKTI^®?

Welcome to the CAR-T patient journey experience, a guide for patients and caregivers brought to you by Janssen Biotech, Incorporated, and Legend Biotech, the developers of CARVYKTI® (ciltacabtagene autoleucel).

CARVYKTI® is a treatment used for adult patients who have cancer of the bone marrow called multiple myeloma. It is used when at least four other kinds of treatment have not worked or have stopped working.

CARVYKTI® is a medicine made from your own white blood cells, which have been changed (genetically modified) to recognize and attack your multiple myeloma cells

CARVYKTI® may cause serious side effects which may be fatal or life threatening including the risk of Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barré Syndrome, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome, and Prolonged Cytopenias.

Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS.

Please see the Important Safety Information in this video and the full Prescribing Information and Medication Guide at CARVYKTI.com. Discuss any questions you have with your doctor.

Hello, my name is Tina, and I am here to provide an overview of what to expect during your CAR-T therapy.

This experience will also provide some useful information to your caregiver on their role throughout the treatment journey.

As you may know, CAR-T stands for…

…Chimeric Antigen Receptor-T cell.

Over the next few minutes, I will explain in detail the five steps of CAR-T therapy.

These include collecting your white blood cells, changing (or genetically modifying) your T cells, pre-infusion treatment, receiving your one-time CARVYKTI® infusion, and undergoing post-infusion monitoring for side effects.

In CAR-T Therapy, your white blood cells are collected, and then your T cells are isolated and modified by a manufacturing facility to change them into your CAR-T cells. While they’re being genetically modified, you may undergo what’s called bridging therapy, which I’ll explain a little later. After being modified, the cells are reintroduced to your body where they are programmed to recognize a protein present on the surface of multiple myeloma cells, as well as some other immune cells.

Remember, your healthcare team is here for you and ready to answer any questions you may have about your specific CAR-T treatment.

Let’s begin.

The first step in CAR-T therapy is cell collection, or leukapheresis.

Your cells will be collected in a leukapheresis room with the assistance of a leukapheresis nurse.

Your blood will be drawn into a machine that separates the white and red blood cells, collects some of the white blood cells, including T cells, and returns the rest of the blood into your body.

This process may take 3 to 6 hours and may need to be repeated.

After you complete the cell collection process, you may be treated with medicines, sometimes referred to as bridging therapy, to control your multiple myeloma so the disease does not worsen while your CAR-T cells are being manufactured.

Bridging therapies are anticancer treatments that are intended to reduce the number of cancer cells in your body. These treatments may take place at home or at a treatment center.

Your healthcare team will let you know if bridging therapy is necessary for you.

Once your white blood cells have been extracted, they are frozen and sent to a manufacturing site. There, the T cells are separated and customized into your ciltacabtagene autoleucel CAR-T cells. This is done by genetically modifying your T cells to be able to recognize B-cell maturation antigens (BCMA) on the surface of multiple myeloma cells. Your CARVYKTI® CAR-T cells are then frozen and sent back to your CARVYKTI® Certified Treatment Center.

This process typically takes around 4 to 5 weeks, but timing and outcomes of manufacturing may vary. Your healthcare team will provide a more specific time frame for you the closer you get to your infusion date.

Remember, your healthcare team is there to help every step of the way, so you and your caregiver should never hesitate to ask questions.

Once your cells have been manufactured, it’s time to begin preparing for your CARVYKTI® infusion.

A few days before your infusion, you’ll receive low-dose chemotherapy infusions with cyclophosphamide and fludarabine.

These infusions will help prepare your body for the CAR-T infusion. Each of these infusions will be given to you once a day for 3 days. These infusions are given to help clear out some of your white blood cells to make the necessary space in your immune system for CARVYKTI®. This is also known as lymphodepleting chemotherapy.

Your healthcare team will guide you through this chemotherapy infusion process.

It is important for you and your caregiver to communicate regularly with your healthcare provider regarding how you are feeling and any symptoms you think you are experiencing.

The day has come. Usually about 4 to 5 weeks after your initial cell collection, and 2 to 4 days after your last low-dose chemotherapy, you will be ready for your CARVYKTI® infusion. Your healthcare team will let you know what to expect and guide you through the process.

Your T cells have been genetically modified at the manufacturing facility…

And will now be returned to your body to fight the multiple myeloma cancer cells. Thirty to 60 minutes before you are given your CAR-T infusion, you may be given other medicines. These may include medicines for an allergic reaction (antihistamines) and medicines for fever (such as acetaminophen).

Your healthcare provider will give you your CARVYKTI® through a one-time intravenous infusion that takes approximately 30 to 60 minutes.

It is helpful to be well-hydrated and to have eaten some food before arriving. It is required that you be accompanied by a caregiver to help throughout this infusion day.

After your infusion of CARVYKTI®, you will be monitored for side effects. Your healthcare team should provide you with a detailed plan, which will be tailored to your needs. In some cases, this will be in collaboration with your primary oncologist.

Caregivers serve as another set of eyes and ears for your healthcare team. They should be observant and keep the contact information of the healthcare team members handy to be able to alert them quickly if they think you are having symptoms of a side effect.

After your infusion of CARVYKTI®, your healthcare providers at the CARVYKTI® Certified Treatment Center will closely monitor you daily for 10 days following infusion for any signs and symptoms of a reaction to treatment.

You should plan to stay close to the location where you received your treatment for at least 4 weeks. Your healthcare provider will check to see that your treatment is working and help you with any side effects that may occur. You may be hospitalized if you develop serious side effects until your side effects are under control and it is safe for you to leave the hospital.

Your healthcare provider will want to do blood tests to follow your progress. It is important that you have your blood tested. If you miss an appointment, call your healthcare provider as soon as possible to reschedule.

After this 4-week monitoring period, your healthcare provider will continue to provide care and partner with you to create a plan for long-term monitoring and regular follow-ups. Let your healthcare providers know if you're not feeling well.

Refrain from driving or hazardous activities for at least 8 weeks following treatment with CARVYKTI®.

You must not be given certain vaccines called live vaccines for some time before and after CARVYKTI® treatment. Talk to your healthcare provider if you need to have any vaccinations.

Do not donate blood, organs, tissues, or cells for transplantation.

CARVYKTI® may cause side effects that are severe or life-threatening and can lead to death. Call your healthcare provider or get emergency help right away if you get any of the following: fever (100.4 degrees Fahrenheit/38 degrees Celsius or higher), chills or shaking chills, fast or irregular heartbeat, difficulty breathing, very low blood pressure, dizziness/light headedness, effects on your nervous system, some of which can occur days or weeks after you receive the infusion, and may initially be subtle such as: feeling confused, less alert or disoriented, having difficulty speaking or slurred speech, having difficulty reading, writing and understanding words, memory loss; loss of coordination affecting movement and balance, slower movements, changes in handwriting; personality changes including a reduced ability to express emotions, being less talkative, disinterest in activities, and reduced facial expression; tingling, numbness and pain of hands and feet, difficulty walking, leg and/or arm weakness, and difficulty breathing; or facial numbness, difficulty moving muscles of face and eyes.

It is important that you tell your healthcare providers that you have received CARVYKTI® and to show them your CARVYKTI® Patient Wallet Card. Your healthcare providers may give you other medicines to treat your side effects.

CARVYKTI® can cause a very common side effect called cytokine release syndrome or CRS, which can be severe or fatal. Symptoms of CRS include fever, difficulty breathing, dizziness or lightheadedness, nausea, headache, fast heartbeat, low blood pressure, or fatigue. Tell your healthcare provider right away if you develop fever or any of these other symptoms after receiving CARVYKTI®.

CARVYKTI® can cause various neurologic side effects, some of which may be severe or fatal. Signs or symptoms associated with neurologic toxicity, some of which may occur days or weeks following the infusion, may include but are not limited to confusion, disorientation, loss of consciousness, seizures, difficulty speaking, reading or writing, tremor, slower movements, changes in personality, depression, tingling and numbness of hands and feet, leg and arm weakness, and facial numbness.

The most common side effects of CARVYKTI® include: fever (100.4 degrees Fahrenheit/38 degrees Celsius or higher), chills, dizziness or light-headedness, headache, muscle or joint pain, feeling very tired; altered mental state, confusion; infections, low levels of antibodies (immunoglobulins) in the blood, cough, being short of breath; diarrhea, nausea, decreased appetite, constipation; fast or irregular heartbeat; and problems with blood clotting.

Other possible side effects include an increased risk of life-threatening infections that may lead to death. Tell your healthcare providers right away if you develop fever, chills, or any signs or symptoms of an infection.

CARVYKTI® can lower one or more types of your blood cells—including red blood cells, white blood cells, or platelets, which are cells that help blood to clot—which may make you feel weak or tired or increase your risk of severe infection or bleeding. After treatment, your healthcare providers will test your blood to check for this. Tell your healthcare providers right away if you get a fever, chills, or any signs or symptoms of an infection, are feeling tired, or have bruising or bleeding.

Having CARVYKTI® in your blood may cause some commercial Human Immunodeficiency Virus (HIV) tests to incorrectly give you an HIV-positive result even though you may be HIV-negative.

These are not all the possible side effects of CARVYKTI®. Tell your healthcare providers if you experience any side effects.

Your caregiver plays a key role in helping you identify and communicate about any symptoms that may suggest you are having a side effect, which you should report to your healthcare team as soon as possible. They may ask you to undergo certain tests to identify particular side effects.

Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy, or REMS, called the CARVYKTI® REMS.

For more information about the CARVYKTI® REMS Program, visit CARVYKTIREMS.com.

We hope this experience has given you a better idea of what to expect during your CARVYKTI® journey. Your healthcare team at the certified treatment center will provide you with the specific course of your care and will be able to answer any questions you have concerning this treatment.

For more information and to discover other resources for patients and caregivers, visit CARVYKTI.com

What is the most important information I should know about CARVYKTI®?

CARVYKTI® may cause side effects that are severe or life-threatening and can lead to death. Call your healthcare provider or get emergency help right away if you get any of the following:

• fever (100.4°F/38°C or higher)
• chills or shaking chills
• fast or irregular heartbeat
• difficulty breathing
• very low blood pressure
• dizziness/lightheadedness
• effects on your nervous system, some of which can occur days or weeks after you receive the infusion, and may initially be subtle such as:
  • feeling confused, less alert or disoriented, having difficulty speaking or slurred speech, having difficulty reading, writing and understanding words, memory loss
  • loss of coordination affecting movement and balance, slower movements, changes in handwriting
  • personality changes including a reduced ability to express emotions, being less talkative, disinterest in activities, and reduced facial expression
  • tingling, numbness and pain of hands and feet, difficulty walking, leg and/or arm weakness, and difficulty breathing
  • facial numbness, difficulty moving muscles of face and eyes

It is important that you tell your healthcare providers that you have received CARVYKTI® and to show them your CARVYKTI® Patient Wallet Card. Your healthcare providers may give you other medicines to treat your side effects.

How will I receive CARVYKTI®?

• CARVYKTI® is made from your own white blood cells, so your blood will be collected by a process called “leukapheresis.” The procedure can take 3 to 6 hours and may need to be repeated
• Your white blood cells are sent to a manufacturing center to make CARVYKTI®. It takes about 4-5 weeks from the time your cells are received at the manufacturing site and are available to be shipped back to your healthcare provider, but the time may vary
• While CARVYKTI® is being made, you may get other medicines to treat the multiple myeloma. This is so that your multiple myeloma does not get worse

Before you get CARVYKTI®, your healthcare provider will give you chemotherapy for 3 days to prepare your body.

30 to 60 minutes before you are given CARVYKTI®, you may be given other medicines. These may include:

• medicines for an allergic reaction (antihistamines)
• medicines for fever (such as acetaminophen)

When your CARVYKTI® is ready, your healthcare provider will give CARVYKTI® to you through a catheter (tube) placed into your vein (intravenous infusion). Your dose of CARVYKTI® will be given in one infusion bag. The infusion usually takes approximately 30-60 minutes.

After getting CARVYKTI®, you will be monitored at the certified healthcare facility where you received your treatment for at least 10 days after the infusion.

You should plan to stay close to the location where you received your treatment for at least 4 weeks. Your healthcare provider will check to see that your treatment is working and help you with any side effects that may occur. You may be hospitalized if you develop serious side effects until your side effects are under control and it is safe for you to leave the hospital.

Your healthcare provider will want to do blood tests to follow your progress. It is important that you have your blood tested. If you miss an appointment, call your healthcare provider as soon as possible to reschedule.

What should I avoid after receiving CARVYKTI®?

Do not drive, or operate heavy machinery, or do other activities that could be dangerous if you are not mentally alert, for at least 8 weeks after you get CARVYKTI®. This is because the treatment can cause memory and coordination problems, sleepiness, confusion, dizziness, seizures, or other neurologic side effects as discussed by your healthcare provider

• You must not be given certain vaccines called live vaccines for some time before and after CARVYKTI® treatment. Talk to your healthcare provider if you need to have any vaccinations
• Do not donate blood, organs, tissues, or cells for transplantation

What are the possible or reasonably likely side effects of CARVYKTI®?

The most common side effects of CARVYKTI® include:

• fever (100.4°F/38°C or higher), chills
• dizziness or lightheadedness
• headache, muscle or joint pain, feeling very tired
• altered mental state, confusion
• infections
• low levels of antibodies (immunoglobulins) in the blood
• cough, being short of breath
• diarrhea, nausea, decreased appetite, constipation
• fast or irregular heartbeat
• problems with blood clotting

CARVYKTI® can cause a very common side effect called cytokine release syndrome or CRS, which can be severe or fatal. Symptoms of CRS include fever, difficulty breathing, dizziness or lightheadedness, nausea, headache, fast heartbeat, low blood pressure, or fatigue. Tell your healthcare provider right away if you develop fever or any of these other symptoms after receiving CARVYKTI®.

CARVYKTI® can increase the risk of life-threatening infections including COVID-19 that may lead to death. Tell your healthcare provider right away if you develop fever, chills, or any signs or symptoms of an infection.

CARVYKTI® can cause various neurologic side effects, some of which may be severe or fatal. Symptoms include but are not limited to confusion, disorientation, loss of consciousness, seizures, difficulty speaking, reading or writing, tremor, slower movements, changes in personality, depression, tingling and numbness of hands and feet, leg and arm weakness, and facial numbness.

CARVYKTI® can lower one or more types of your blood cells (red blood cells, white blood cells, or platelets [cells that help blood to clot]), which may make you feel weak or tired, or increase your risk of severe infection or bleeding that may lead to death. After treatment, your healthcare provider will test your blood to check for this. Tell your healthcare provider right away if you get a fever, chills, or any signs or symptoms of an infection, are feeling tired, or have bruising or bleeding.

Having CARVYKTI® in your blood may cause some commercial Human immunodeficiency virus (HIV) tests to incorrectly give you an HIV-positive result even though you may be HIV-negative.

These are not all the possible side effects of CARVYKTI®. Call your healthcare provider if you have any side effect.

You may report side effects to FDA at 1-800-FDA-1088.