Yescarta

Yescarta is used to treat large B-cell lymphoma and relapsed or refractory follicular lymphoma (FL) in adults. Yerscarta (axicabtagene ciloleucel) is a personalized CAR T-cell cancer treatment made from your own T-cells, given as a one-time intravenous infusion.

Yescarta is made by collecting your T-cells and genetically modifying them in a laboratory to express a chimeric antigen receptor (CAR). These enhanced CAR T-cells specifically target and destroy cancer cells displaying the CD19 protein, strengthening your immune system's cancer-fighting ability.

Yescarta (axicabtagene ciloleucel) gained FDA approval on October 18, 2017. There is no generic.

Yescarta is FDA-approved for adults with:

• Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
• Relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma
• Relapsed or refractory follicular lymphoma (FL) after 2 or more lines of systemic therapy. This indication is approved under accelerated approval based on the response rate. Continued approval for this indication may be contingent upon verification and description of a clinical benefit being shown in confirmatory trials.

Since Yescarta is made from your white blood cells, your blood will be collected by a process called “leukapheresis” (loo-kah-fur-ee-sis), which will concentrate your white blood cells.

• Your blood cells will be sent to a manufacturing center to make your Yescarta.
• Before you get Yescarta, you will get 3 days of chemotherapy to prepare your body.

When your Yescarta is ready, your healthcare provider will give it to you through a catheter placed into your vein (intravenous infusion). The infusion usually takes less than 30 minutes.

• You will be monitored where you received your treatment daily for at least 7 days after the infusion.
• You should plan to stay close to a certified healthcare facility for at least 4 weeks after getting Yescarta. Your healthcare provider will help you with any side effects that may occur.
• You may be hospitalized for side effects, and your healthcare provider will discharge you if 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. If you miss an appointment, call your healthcare provider as soon as possible to reschedule.

Tell all your healthcare providers that you have received Yescarta and show them your Yescarta Patient Wallet Card. Your healthcare provider may give you other medicines to treat your side effects. Yescarta is different than other cancer medicines because it is made from your white blood cells, which have been modified to recognize and attack your lymphoma cells.

Yescarta may cause side effects that are life-threatening and can lead to death and carries a Boxed Warning for cytokine release syndrome, neurologic toxicities, and secondary blood cancers.

Cytokine Release Syndrome (CRS): A potentially life-threatening condition where the immune system overreacts and releases excessive amounts of cytokines, leading to widespread inflammation and organ dysfunction. Tell your healthcare provider immediately if you develop symptoms such as fever, low blood pressure, trouble breathing, or vomiting. Talk to your healthcare provider about having medication available to quickly treat this condition.

Brain/Nervous System Effects: The treatment can cause confusion, seizures, difficulty speaking, or other brain problems. These neurological symptoms can be serious or fatal.

T Cell Cancer Risk: Rarely, the modified immune cells used in treatment can themselves become cancerous, creating a new type of blood cancer different from the original disease being treated.

Call or see your healthcare provider or get emergency help right away if you get any of the following:

• Fever (100.4°F/38°C or higher)
• Difficulty breathing
• Chills or shaking chills
• Confusion
• Dizziness or lightheadedness
• Severe nausea, vomiting, or diarrhea
• Fast or irregular heartbeat
• Severe fatigue or weakness.

It is important to tell your healthcare provider that you received Yescarta. Your healthcare provider may giveyou other medicines to treat your side effects.

Before receiving Yescarta, tell your healthcare provider about all your medical problems, including if you have or have had:

• Neurologic problems (such as seizures, stroke, or memory loss)
• Lung or breathing problems
• Heart problems
• Liver problems
• Kidney problems
• A recent or active infection.

Tell your healthcare provider if you are pregnant or intend to become pregnant, or if you are breastfeeding.

Also, tell your doctor if you have received a vaccine in the past 2 weeks. Vaccination with live virus vaccines is not recommended for at least 6 weeks before the start of lymphodepleting chemotherapy, during treatment, and until your immune system recovers following treatment with Yescarta.

Pregnancy

If you are a woman of childbearing potential, your healthcare provider may conduct pregnancy testing before receiving this medicine. You may also need to use birth control to prevent pregnancy during and shortly after treatment with Yescarta and chemotherapy.

If you receive Yescarta 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.

Breastfeeding

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

Common Side Effects

The most common side effects of Yescarta are:

• Fever (100.4°F/38°C or higher)
• Low white blood cells (can occur with a fever)
• Low red blood cells
• Low blood pressure (dizziness or lightheadedness, headache, feeling tired, short of breath)
• Fast heartbeat
• Confusion
• Difficulty speaking or slurred speech
• Nausea
• Diarrhea.

Yescarta may increase your risk of getting cancers, including certain types of blood cancers. Your healthcare provider should monitor you for this.

Other Serious Side Effects

Yescarta may also cause other serious side effects:

• Hypersensitivity (allergic) reactions, including anaphylaxis, may occur during a Yescarta infusion. These may be due to dimethyl sulfoxide (DMSO) or the residual gentamicin in the infusion
• Serious infections. Your healthcare provider will monitor you for these. Report any signs of an infection (such as fever, chills, difficulty breathing, swelling, pain, redness, or urinary problems) to a doctor.
• Life-threatening nerve problems. including encephalopathy (a disturbance in your brain function), headache, tremor, dizziness, speech difficulties, delirium, and insomnia
• Prolonged cytopenias (low blood cell levels), such as neutropenia, thrombocytopenia, and anemia, may persist for several weeks following a Yescarta infusion
• Low levels of immunoglobulins in your blood (hypogammaglobulinemia) and B-cell aplasia can occur in Yescarta-treated patients. Your healthcare provider will monitor your immunoglobulin levels.

These are not all the possible side effects of Yescarta. Call your healthcare provider about any side effects that concern you. You may report side effects to the FDA at 1-800-FDA-1088.

Approval for Yescarta was based on positive results from clinical trials.

• The ZUMA-1 (NCT02348216) clinical trial in patients with refractory large B-cell lymphoma (LBCL) reported an 83% objective response rate (ORR), 58% complete response (CR) rate, and a 5-year overall survival (OS) rate of 43%. Among five-year survivors, 92% required no additional treatment.
• The ZUMA-7 (NCT03391466) demonstrated Yescarta's superiority over standard stem cell transplant in r/r FL patients, reducing death risk by 27.4% and improving event-free survival compared with standard care.

Dose of Yescarta for large B-cell lymphoma or FL in adults

Three days before your Yescarta infusion, you will receive a lymphodepleting regimen of cyclophosphamide and fludarabine.

On the day of your infusion, your healthcare provider will:

• Verify your identity
• Premedicate with acetaminophen and an H1-antihistamine
• Confirm the availability of tocilizumab before infusion
• Infuse a target Yescarta dose of 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells, within 30 minutes.

Avoid driving for at least 2 weeks after you get Yescarta.

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

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

• Systemic corticosteroids may interfere with the activity of this drug.

See the Yescarta Prescribing Information for a complete list of interactions.

Active: axicabtagene ciloleucel

Inactive: albumin (human), DMSO (dimethylsulfoxide).

Yescarta is supplied in an infusion bag (NDC 71287-119-01) containing approximately 68 mL of frozen suspension of genetically modified autologous T cells in 5% DMSO and 2.5% albumin (human).

The target Yescarta dose contains 2 × 106 CAR-positive viable T cells per kg of body weight, with a maximum of 2 × 108 CAR-positive viable T cells in approximately 68 mL.

Yescarta is made by Kite Pharma, Inc., Santa Monica, CA 90404.