Ciltacabtagene Autoleucel (Carvykti®)

Ciltacabtagene autoleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous (self-directed) T-cell immunotherapy used to treat some types of cancer. T cells, a part of your immune system, are removed from your body through an intravenous (IV) line by a process called leukapheresis. In a lab, a chimeric antigen receptor (CAR) is added to your T cells. These T cells are put back into your body. CAR gives the T cells the ability to identify, attack, and kill cancer cells. 

How to take Ciltacabtagene Autoleucel

Ciltacabtagene autoleucel is given through an intravenous (IV) infusion and your dose will be personalized to you. You will be given a chemotherapy regimen before getting this infusion to prepare your body for treatment. Before the ciltacabtagene autoleucel infusion, you will be given pre-medications including acetaminophen (Tylenol) and an H1 antihistamine such as diphenhydramine (Benadryl) to prevent a reaction. Some people do have reactions like fevers, chills, shaking, higher than normal heart rate, rash, low blood pressure, shortness of breath, cough, chest tightness, or wheezing. If you have any changes in how you are feeling, tell your provider right away.

 Ciltacabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI REMS. This ensures that the facility where you are receiving this medication is qualified to administer the medication and has the required supportive medications available to treat side effects if you should need them.

You will be in the hospital until you have recovered from any serious side effects you are having. Depending on where you received your treatment and how you are doing, you may be asked to stay within 2 hours of the treatment center for several weeks. Your providers will monitor your recovery closely.

Possible Side Effects

There are a number of things you can do to manage the side effects of ciltacabtagene autoleucel. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:

Cytokine Release Syndrome

After receiving ciltacabtagene autoleucel, large numbers of white blood cells are activated and release inflammatory cytokines which can lead to cytokine release syndrome, sometimes severe cases are referred to as cytokine storms. Signs include high fever, lower than normal blood pressure, difficulty breathing, severe nausea and vomiting, severe diarrhea, chills/shaking, severe muscle and joint pain, and bleeding. This serious side effect can happen up until 4 weeks after the infusion. You should call your provider immediately if you have any signs or symptoms of cytokine release syndrome so that appropriate treatment can be given.

Neurologic Toxicity including ICANS

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a neurological side effect that impacts the way the nervous system works. Neurological (brain) toxicities, such as aphasia (being unable to understand speech or speak normally), a change in mental status, encephalopathy (lack of blood flow and oxygen to your brain), and seizures have happened in patients who received this medication. Other neurological side effects can include headaches, neuropathy (numbness or tingling), and/or changes to your motor skills (loss of control, often of the arms or legs). Your care team will be monitoring you very closely for any changes in your mental status.

There is also a risk of Guillain-Barré syndrome with this medication, where your immune system attacks nerves in your body. If you have new or worsening numbness or tingling that starts in your lower body and continues to your upper body, confusion, weakness, or problems with balance, call your care team right away.

This medication can also cause Parkinsonism which causes movements such as shaking, body stiffness, and trouble moving or keeping your balance.

You should not drive or operate heavy machinery for at least 8 weeks after the medication is given. This medication can cause side effects that can affect your ability to do these tasks.

Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome

This is a rare but serious side effect that causes inflammation of the immune system. If you have persistent fevers, fatigue, headache, feel foggy, enlarged lymph nodes, enlarged liver and spleen, bleeding, clotting issues, rash, change in blood pressure or heart rate, liver is not working right, or low blood counts, contact your provider right away.

Hypogammaglobulinemia

This medication can cause lowered levels of immunoglobulin. Your levels will be monitored and immunoglobulin will be administered as needed. While your levels are low, you are at an increased risk of getting an infection. Be sure to follow the recommendations above to decrease the chance of an infection. You should not receive any vaccines without talking with your oncology team first.

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your oncology care team know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion.

Infection and Low White Blood Cell Count (Leukopenia/Neutropenia)

This medication can cause life-threatening infections, with or without a decrease in white blood cell counts.

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4 °F or 38°C), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips to preventing infection:

•  Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
• Avoid large crowds and people who are sick (i.e.: those who have a cold, fever, or cough or live with someone with these symptoms).
• When working in your yard, wear protective clothing including long pants and gloves.
• Do not handle pet waste.
• Keep all cuts or scratches clean.
• Shower or bathe daily and perform frequent mouth care.
• Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
• Ask your oncology care team before scheduling dental appointments or procedures.

Ask your oncology care team before you, or someone you live with has any vaccinations.

Low Platelet Count (Thrombocytopenia)

Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your oncology care team know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums, or blood in your urine or stool. If the platelet count becomes too low, you may receive a transfusion of platelets.

• Do not use a razor (an electric razor is fine).
• Avoid contact sports and activities that can result in injury or bleeding.
• Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib) etc. as these can all increase the risk of bleeding. Please consult with your healthcare team regarding use of these agents and all over the counter medications/supplements while on therapy.
• Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.

This medication can also cause coagulopathy which means that your blood may have a hard time forming clots.

Secondary Cancers

A secondary cancer is one that develops as a result of cancer treatment for another cancer. This is quite rare, but you should be aware of the risk. In most cases, a secondary cancer related to chemotherapy is a blood cancer (leukemia, myelodysplastic syndrome [MDS]), which can happen months to years after treatment. This medication can also cause a secondary T cell malignancy (cancer), which can happen as soon as weeks after treatment. Your provider will monitor your labs closely. Consider having a complete blood count with differential checked annually by your healthcare provider for the rest of your life to monitor for secondary cancers.

Fatigue

Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team for helpful tips on dealing with this side effect.

Muscle or Joint Pain/Aches and Headache

Ciltacabtagene autoleucel can cause joint or muscle aches and pains, which can interfere with quality of life. Be sure to talk to your oncology care team if you develop this side effect. Be sure to discuss which pain relievers you can safely take with your oncology team, as these are not without their own side effects.

Decrease in Appetite

Nutrition is an important part of your care. Cancer treatment can affect your appetite and, in some cases, the side effects of treatment can make eating difficult. Ask your oncology care team about nutritional counseling services at your treatment center to help with food choices.

• Try to eat five or six small meals or snacks throughout the day, instead of 3 larger meals.
• If you are not eating enough, nutritional supplements may help.
• You may experience a metallic taste or find that food has no taste at all. You may dislike foods or beverages that you liked before receiving cancer treatment. These symptoms can last for several months or longer after treatment ends.
• Avoid any food that you think smells or tastes bad. If red meat is a problem, eat chicken, turkey, eggs, dairy products, and fish without a strong smell. Sometimes cold food has less of an odor.
• Add extra flavor to meat or fish by marinating it in sweet juices, sweet and sour sauce, or dressings. Use seasonings like basil, oregano, or rosemary to add flavor. Bacon, ham, and onion can add flavor to vegetables.

Diarrhea

Your oncology care team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole grain breads, cereals, and seeds. Soluble fiber is found in some foods and absorbs fluid, which can help relieve diarrhea. Foods high in soluble fiber include: applesauce, bananas (ripe), canned fruit, orange sections, boiled potatoes, white rice, products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses of non-alcoholic, un-caffeinated fluid a day to prevent dehydration.

Constipation

There are several things you can do to prevent or relieve constipation. Include fiber in your diet (fruits and vegetables), drink 8-10 glasses of non-alcoholic fluids a day, and keep active. A stool softener once or twice a day may prevent constipation. If you do not have a bowel movement for 2-3 days, you should contact your healthcare team for suggestions to relieve the constipation.

Tachycardia

This therapy can cause increased heart rate, also called tachycardia. You may feel like your heart is racing, chest pain, lightheaded, or short of breath. Call your care provider if you are experiencing any of these side effects.

Nausea and Vomiting

Talk to your oncology care team so they can prescribe medications to help you manage nausea and vomiting. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy, or acidic foods (lemons, tomatoes, oranges). Try saltines, or ginger ale to lessen symptoms.

Call your oncology care team if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Low Blood Pressure (Hypotension)

Ciltacabtagene autoleucel may cause low blood pressure, especially in patients who have certain heart problems. Get up slowly when standing from a sitting or sleeping position to avoid low blood pressure. Let your care team know if you are having symptoms of low blood pressure which may include dizziness, lightheadedness, or blurred vision.

Swelling (Edema)

This therapy can cause a buildup of fluid and swelling (edema) in the face, especially around the eyes, and extremities (arms and legs). It may also cause a buildup of fluid and swelling in the lower abdomen (belly). This can be a sign of other problems, so be sure to report any abnormal swelling to your healthcare team for further testing.

 Less common but important side effects can include:

• Allergic (Hypersensitivity) Reaction: In some cases, patients can have an allergic reaction to this therapy. Signs of a reaction can include: shortness of breath or difficulty breathing, rash, and flushing. If you notice any changes in how you feel during the infusion, let your nurse know immediately. The infusion will be slowed or stopped if this occurs. Depending on the severity of your reaction, you may still be able to receive the therapy with a pre-medication to prevent a reaction, or if the therapy is given at a slower rate.

Reproductive Concerns

Exposure of an unborn child to this therapy could cause birth defects, so you should not become pregnant or father a child while on this therapy or for a year after having received it. Effective birth control is necessary during treatment. Even if your menstrual cycle stops or you believe you are not producing sperm, you could still be fertile and conceive. You should consult with your healthcare team before breastfeeding while receiving this therapy.