Kymriah (tisagenlecleucel) is an individualized CAR-T cell therapy that may be used to treat:

• Adults with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy (but not for patients with primary CNS lymphoma)
• Adults with r/r follicular lymphoma (FL) after two or more lines of systemic therapy
• Children and young adults up to and including 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Kymriah is an immune cellular therapy that only targets your B cells and B-cell precursors to help your immune system kill cancer cells. It is typically given as a single infusion after a short 4-day course of chemotherapy which prepares your body for the Kymriah infusion.

It is available only through a restricted program called the Kymriah Risk Evaluation and Mitigation Strategy (REMS). It must be ordered through a qualified Kymriah Treatment Center.

Kymriah was approved on August 30, 2017.

Kymriah may cause a serious side effect called cytokine release syndrome, which causes fever, chills, trouble breathing, vomiting, and other symptoms, and can be potentially life-threatening. Your caregivers will have medication available to quickly treat this condition if it occurs.

It can also cause life-threatening nerve problems. Tell your caregivers or seek emergency medical attention if you have problems with speech, problems with thinking or memory, confusion, or a seizure.

Monitor for hypersensitivity reactions during the infusion.

Kymriah may cause serious infections. Monitor for signs and symptoms.

Other serious side effects include Grade 3 and above cytopenias, prolonged neutropenias, and hypogammaglobulinemias.

Secondary malignancies should be reported to Novartis Pharmaceuticals Corporation at 1-844-4Kymriah.

Do not drive, operate machinery or partake in hazardous tasks for at least 8 weeks after receiving Kymriah.

The dosage of Kymriah varies depending on the condition being treated and the age of the patient.

For at least 4 weeks, plan to stay near the hospital or clinic where you received Kymriah. Avoid being so far away that it takes you longer than 2 hours to travel back to the hospital.

Serious and sometimes fatal infections may develop after the injection. Call your doctor right away if you have a fever, chills, easy bruising, unusual bleeding, or other signs of infection.

Your doctor will consider premedication with acetaminophen and diphenhydramine or another H1-antihistamine approximately 30 to 60 minutes before infusion. Avoid using corticosteroids at any time except in the case of a life-threatening emergency.

Adults with r/r diffuse large B-cell lymphoma or follicular lymphoma

• Administer 0.6 to 6.0 x 10⁸ CAR-positive viable T-cells intravenously

May be suspended in one to three patient-specific infusion bags for IV administration.

B-cell precursor ALL

• Above 50kg: Administer 0.1 to 2.5 x 10⁸ total CAR-positive viable T-cells (non-weight based) intravenously
• 50kg or less: Administer 0.2 to 5.0 x 10⁶ CAR-positive viable T-cells per kg body weight intravenously

May be suspended in one to three patient-specific infusion bags for IV administration.

To make sure Kymriah is safe for you, tell your doctor if you have ever had:

• hepatitis B or C;
• HIV (human immunodeficiency virus); or
• if you have received a vaccine in the past 2 weeks.

Women may need pregnancy testing before receiving this medicine. You may also need birth control to prevent pregnancy during and shortly after treatment with Kymriah and chemotherapy.

If you receive Kymriah during pregnancy, your baby's blood may need to be tested after it is born. This is to evaluate any effects the medicine may have had on the baby.

It may not be safe to breastfeed while using Kymriah. Ask your doctor about any risks.

Call your doctor for instructions if you miss any of your chemotherapy treatment, or if you miss a dose of your premedications to prevent side effects of Kymriah.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

This medicine can cause weakness, drowsiness, confusion, problems with memory or coordination, and seizures. Avoid driving or operating machinery for at least 8 weeks after you are treated with Kymriah.

Do not donate blood, an organ, or any tissues or cells from your own body.

Do not receive a "live" vaccine while using Kymriah, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Kymriah may cause hypersensitivity reactions. Get emergency medical help if you have signs of an allergic reaction such as hives; difficulty breathing; or swelling of your face, lips, tongue, or throat.

A serious side effect of Kymriah is called cytokine release syndrome (CRS). Tell your caregivers right away if you have signs of this condition: fever, chills, trouble breathing, body aches, vomiting, diarrhea, or feeling light-headed. Your caregivers will have medication available to quickly treat CRS if it occurs.

Also, tell your caregivers or seek emergency medical attention if you have signs of life-threatening nerve problems: problems with speech, problems with thinking or memory, confusion, or a seizure.

This medicine can cause you to have a false positive screening test for HIV (human immunodeficiency virus). Tell any doctor who treats you that you are using Kymriah.

Using Kymriah may increase your risk of developing other types of cancer, or causing your leukemia to come back. Your doctor will need to check your progress for the rest of your life.

If you have ever had hepatitis B, Kymriah can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

Also, call your doctor at once if you have:

• agitation
• anxiety
• bleeding or bruises
• headaches
• signs of infection - fever, chills, flu symptoms, mouth sores, skin sores, easy bruising or bleeding, cough, trouble breathing
• tremors
• trouble speaking or understanding what is said to you
• unusual thoughts or behavior
• unusual tiredness.

Common Kymriah side effects may include:

• bleeding
• cough
• decreased appetite
• edema
• encephalopathy
• fast heartbeats
• fatigue
• fever
• gastrointestinal effects, such as nausea, vomiting, diarrhea, loss of appetite
• headache, confusion, feeling tired
• infections
• low blood pressure
• musculoskeletal pain
• nausea and vomiting.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may interact with tisagenlecleucel, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.