Special Alert:

The Food and Drug Administration (FDA) has received reports of T-cell malignancies, including chimeric antigen receptor CAR-positive lymphoma, in patients who received treatment with BCMA- or CD19-directed autologous CAR T cell immunotherapies such as tisagenlecleucel injection.  At this time, benefits still outweigh the risks, but your doctor will monitor you during and after receiving treatment. Talk to your doctor about any concerns you have regarding your treatment.

Tisagenlecleucel injection may cause a serious or life-threatening reaction called cytokine release syndrome (CRS). A doctor or nurse will monitor you carefully during your infusion and for at least 4 weeks afterwards. Tell your doctor if you have an inflammatory disorder or if you have or think you may have any type of infection now. You will be given medications 30 to 60 minutes before your infusion to help prevent reactions to tisagenlecleucel. If you experience any of the following symptoms during and after your infusion, tell your doctor immediately: fever, chills, shaking, cough, diarrhea, muscle or joint pain, tiredness, difficulty breathing, shortness of breath, confusion, nausea, vomiting, dizziness, or lightheadedness.

Tisagenlecleucel injection may cause severe or life-threatening nervous system reactions. If you experience any of the following symptoms, tell your doctor immediately: headache, restlessness, confusion, anxiety, difficulty falling asleep or staying asleep, uncontrollable shaking of a part of the body, loss of consciousness, agitation, seizures, pain or numbness in an arm or leg, loss of balance, difficulty understanding, or difficulty speaking.

Tisagenlecleucel injection is only available through a special restricted distribution program. A program called Kymriah REMS (Risk Evaluation and Mitigation Strategy) has been set up because of the risks of CRS and neurological toxicities. You can only receive the medication from a doctor and healthcare facility that participates in the program. Ask your doctor if you have any questions about this program.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with tisagenlecleucel. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide.

Tisagenlecleucel injection is used to treat certain acute lymphoblastic leukemia (ALL; also called acute lymphoblastic leukemia and acute lymphatic leukemia; a type of cancer that begins in the white blood cells) in people 25 years of age or younger that has returned or is unresponsive to other treatment(s). It is also used to treat a certain type of non-Hodgkin’s lymphoma (type of cancer that begins in a type of white blood cells that normally fights infection) and follicular lymphoma (FL; a slow-growing cancer that begins in the white blood cells) in adults that has returned or is unresponsive after treatment with at least two other medications. Tisagenlecleucel injection is in a class of medications called autologous cellular immunotherapy, a type of medication prepared using cells from the patient’s own blood. It works by causing the body’s immune system (a group of cells, tissues, and organs that protects the body from attack by bacteria, viruses, cancer cells, and other substances that cause disease) to fight the cancer cells.

Tisagenlecleucel injection comes as a suspension (liquid) to be injected intravenously (into a vein) by a doctor or nurse in a doctor’s office or infusion center. It is usually given over a period of up to 60 minutes as a one-time dose. Before you receive your tisagenlecleucel dose, your doctor or nurse will administer other chemotherapy medications to prepare your body for tisagenlecleucel.

About 3 to 4 weeks before your dose of tisagenlecleucel injection is to be given, a sample of your white blood cells will be taken at a cell collection center using a procedure called leukapheresis (a process that removes white blood cells from the body). This procedure will take about 3 to 6 hours and may need to be repeated. Because this medication is made from your own cells, it must be given only to you. It is important to be on time and to not to miss your scheduled cell collection appointment(s) or to receive your treatment dose. You should plan to stay within 2 hours of the location where you received your tisagenlecleucel treatment for at least 4 weeks after your dose. Your healthcare provider will check to see if your treatment is working and monitor you for any possible side effects. Talk to your doctor about how to prepare for leukapheresis and what to expect during and after the procedure.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before receiving tisagenlecleucel injection,

• tell your doctor and pharmacist if you are allergic to tisagenlecleucel, any other medications, dimethyl sulfoxide (DMSO), dextran 40, or any other ingredients in tisagenlecleucel injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: steroids such as dexamethasone, methylprednisolone (Medrol), prednisolone, and prednisone (Rayos). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have ever had reactions from previous chemotherapy treatments such as breathing problems or irregular heartbeat. Also, tell your doctor if you have or have ever had hepatitis B or C (a virus that infects the liver and may cause severe liver damage), human immunodeficiency virus (HIV), lung, kidney, heart, or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. You will need to have a pregnancy test before you start tisagenlecleucel treatment. If you become pregnant while receiving tisagenlecleucel injection, call your doctor immediately. Tisagenlecleucel injection may cause fetal harm.
• you should know that tisagenlecleucel injection may make you drowsy and cause confusion, weakness, dizziness, and seizures. Do not drive a car or operate machinery for at least 8 weeks after your tisagenlecleucel dose.
• do not donate blood, organs, tissues, sperm, or cells for transplantation after you receive tisagenlecleucel injection.
• check with your doctor to see if you need to receive any vaccinations. Do not have any vaccinations without talking to your doctor for at least 6 weeks before starting chemotherapy, during your tisagenlecleucel treatment, and until your doctor tells you that your immune system has recovered.

Unless your doctor tells you otherwise, continue your normal diet.

If you miss the appointment to collect your cells, you must call your doctor and the collection center right away. If you miss the appointment to receive your tisagenlecleucel dose, you must call your doctor right away.

Tisagenlecleucel injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• constipation
• stomach pain
• back pain
• nasal congestion
• decreased appetite
• weight loss

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately or get emergency medical treatment:

• unusual bleeding or bruising, blood in urine, red or tarry black bowel movements, vomiting blood or material that looks like coffee grounds
• fever, chills, or other signs of infection
• weakness, feeling tired, or shortness of breath
• decreased urination frequency or amount
• swelling of the eyes, face, lips, tongue, throat, arms, hands, feet, ankles, or lower legs
• difficulty swallowing
• rash
• hives
• itching

Tisagenlecleucel injection may increase your risk of developing certain cancers. Talk to your doctor about the risks of receiving this medication.

Tisagenlecleucel injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep all appointments with your doctor, the cell collection center, and the laboratory. Your doctor may order certain lab tests before, during, and after your treatment to check your body’s response to tisagenlecleucel injection.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are receiving tisagenlecleucel injection. This medication may affect the results of certain laboratory tests. Tisagenlecleucel injection can also cause false-positive results with certain HIV tests.

Ask your pharmacist any questions you have about tisagenlecleucel injection.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

• Kymriah^®