Tisagenlecleucel

What is Tisagenlecleucel?

Tisagenlecleucel (Kymriah) is a CD19-directed genetically modified autologous T-cell immunotherapy used for the treatment of:

• B-cell acute lymphoblastic leukemia

• B-cell non-Hodgkin lymphoma (NHL), including the following types:
• Diffuse large B-cell lymphoma (DLBCL).
• DLBCL in patients who had follicular lymphoma.
• High-grade B-cell lymphoma.
• Follicular lymphoma.

What are the uses of this medicine?

• Tisagenlecleucel (Kymriah) is made from your own white blood cells and is a prescription cancer treatment used in patients up to 25 years old who have acute lymphoblastic leukemia (ALL) that is either relapsing (went into remission, then came back) or refractory (did not go into remission after receiving other leukemia treatments).
• It is also used in patients with large B-cell lymphoma or follicular lymphoma, two types of non-Hodgkin lymphoma, that have relapsed or are refractory after having at least two other kinds of treatment.

Limitations of Use:

• Kymriah is not indicated for treatment of patients with primary central nervous system lymphoma.

How does this medicine work?

• Kymriah is made using a patient’s T cells (a type of immune system cell).
• A gene for a special receptor called chimeric antigen receptor (CAR) is added to the T cells in the laboratory.
• These changed T cells called CAR T cells are grown in large numbers in the laboratory and given to the patient by infusion.
• Upon transfusion, tisagenlecleucel direct the T lymphocytes to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells.
• The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19 and the inclusion of this signaling domain may increase the antitumor activity compared to the inclusion of the CD3-zeta chain alone.
• CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
• CD3-zeta (or CD247) is a transmembrane signaling adaptor polypeptide that regulates the assembly of complete TCR complexes and their expression on the cell surface.

Who Should Not Use this medicine ?

Limitations of Use:

• Kymriah is not indicated for treatment of patients with primary central nervous system lymphoma.

What drug interactions can this medicine cause?

• 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 the medications listed above and any of the following:

• steroids such as dexamethasone, methylprednisolone (Medrol), prednisolone, and prednisone (Rayos)

Is this medicine FDA approved?

• In August 2017, Tisagenlecleucel (Kymriah) became the first FDA-approved treatment that included a gene therapy step in the United States.

How should this medicine be used?

Recommended dosage: Pediatric and Young Adult B-cell ALL (up to 25 years of age):

• A single dose of Kymriah contains 0.2 to 5.0 x 106 CAR-positive viable T cells per kg of body weight.

Based on the patient weight reported at the time of leukapheresis:

• Patients 50 kg or less: administer 0.2 to 5.0 x 106 CAR-positive viable T cells per kg body weight.
• Patients above 50 kg: administer 0.1 to 2.5 x 108 CAR-positive viable T cells.

Adult Relapsed or Refractory Diffuse Large B-cell Lymphoma and Follicular Lymphoma:

• Kymriah is provided as a single-dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive viable T cells.
• For adult patients: administer 0.6 to 6.0 x 108 CAR-positive viable T cells.

Administration:

• 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.
• Since Kymriah is made from your own white blood cells, your healthcare provider has to take some of your blood. This is called “leukapheresis.” It takes 3 to 6 hours and may need to be repeated. A tube (intravenous catheter) will be placed in your vein to collect your blood.
• Your blood cells are frozen and sent to the manufacturing site to make Kymriah. It takes about 3-4 weeks from the time your cells are received at the manufacturing site and shipped back to your healthcare provider, but the time may vary.
• While waiting for Kymriah to be made, your healthcare provider may give you therapy to stabilize your cancer.
• In addition, before you get Kymriah, your healthcare provider may give you chemotherapy for a few days to prepare your body.
• When your body is ready, your healthcare provider will give you Kymriah through a tube (intravenous catheter) in your vein. This usually takes less than one hour.
• You should plan to stay within 2 hours of the location where you received your treatment for at least 4 weeks after getting Kymriah.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As a single dose of Kymriah contains 0.2 to 5.0 x 106 CAR-positive viable T cells per kg of body weight for patients 50 kg and below or 0.1 to 2.5 x 108 CAR-positive viable T cells for patients above 50 kg, suspended in one to three patient-specific infusion bag(s)
• A single dose of Kymriah contains 0.6 to 6.0 x 108 CAR-positive viable T cells suspended in one to three patient-specific infusion bag(s) for intravenous infusion.

This medicine is available in fallowing brand namesː

• Kymriah

What side effects can this medication cause?

The most common side effects of this medicine include:

• difficulty breathing
• fever (100.4°F/38°C or higher)
• chills/shaking chills
• confusion
• severe nausea, vomiting, diarrhea
• severe muscle or joint pain
• very low blood pressure
• dizziness/lightheadedness
• headache

• Kymriah can increase the risk of life-threatening infections that may lead to death.
• Kymriah can lower one or more types of your blood cells (red blood cells, white blood cells, or platelets).
• Having Kymriah in your blood may cause a false-positive HIV test result by some commercial tests.

What special precautions should I follow?

• Do not drive, operate heavy machinery, or do other dangerous things for 8 weeks after you get Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness, and seizures.
• Do not donate blood, organs, tissues, sperm, oocytes, and other cells.
• Allergic reactions may occur with infusion of Kymriah. Monitor for hypersensitivity reactions during infusion.
• Infections, including life-threatening or fatal infections, occurred following treatment with Kymriah. Monitor patients for signs and symptoms of infection; treat appropriately.
• Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Kymriah infusion. Patients may exhibit ≥ Grade 3 cytopenias for several weeks following Kymriah infusion. Prolonged neutropenia has been associated with increased risk of infection.
• Hypogammaglobulinemia and agammaglobulinemia related to B-cell aplasia can occur in patients after Kymriah infusion. Monitor and provide replacement therapy until resolution. Assess immunoglobulin levels in newborns of mothers treated with Kymriah.
• Patients treated with Kymriah may develop secondary malignancies or recurrence of their cancer. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs after treatment with Kymriah, contact Novartis Pharmaceuticals Corporation at 1-844-4KYMRIAH.
• CRS, including fatal or life-threatening reactions, occurred following treatment with Kymriah. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.
• Neurological toxicities, including severe or life-threatening reactions, occurred following treatment with Kymriah. Monitor patients 2-3 times during the first week following Kymriah infusion at the REMS-certified healthcare facility for signs and symptoms of neurologic toxicities.
• Because of the risk of CRS and neurological toxicities, Kymriah is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Kymriah REMS.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• There are no available data with Kymriah use in pregnant women.
• It is not known if Kymriah has the potential to be transferred to the fetus.
• Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia.
• Therefore, Kymriah is not recommended for women who are pregnant.

Can this medicine be used in children?

• The safety and efficacy of Kymriah in pediatric patients with r/r DLBCL and r/r FL have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• TISAGENLECLEUCEL

Inactive ingredients:

• DIMETHYL SULFOXIDE
• ALBUMIN HUMAN
• DEXTRAN 40

Who manufactures and distributes this medicine?

Manufactured and Distributed by:

• Novartis Pharmaceuticals Corporation, East Hanover, New Jersey

What should I know about storage and disposal of this medication?

• Store infusion bag(s) in a temperature-monitored system less than or equal to minus 120°C, e.g., in the vapor phase of liquid nitrogen.
• Use closed, break-proof, leak-proof containers when transporting infusion bags within the facility.
• Thaw Kymriah prior to infusion.

• Dailymed label info on Tisagenlecleucel
• FDA Tisagenlecleucel

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