Tisagenlecleucel

Tisagenlecleucel is a prescription medication used for the treatment of acute lymphoblastic leukemia, large B-cell lymphoma, and follicular lymphoma. 

• Tisagenlecleucel is available under the following different brand names: Kymriah.

Common side effects of tisagenlecleucel include:

• Nausea,
• Vomiting,
• Diarrhea,
• Loss of appetite,
• Fever,
• Headache,
• Confusion,
• Tiredness,
• Bleeding, and
• Fast heartbeats

Serious side effects of tisagenlecleucel include:Hives,

• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Fever,
• Chills,
• Trouble breathing,
• Body aches,
• Vomiting,
• Diarrhea,
• Lightheadedness,
• Headaches,
• Unusual tiredness,
• Tremors,
• Anxiety,
• Agitation,
• Unusual thoughts or behavior,
• Trouble speaking or understanding speech,
• Flu symptoms,
• Mouth sores,
• Skin sores,
• Easy bruising,
• Unusual bleeding, and
• Cough

Rare side effects of tisagenlecleucel include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

• Single-dose units contain specific amounts of T-cells depending on the patient’s body weight that is suspended in a patient-specific infusion bag.
• See the certificate of analysis (CoA) for actual cell count following individual preparation.
• Injection, and suspension for pediatric and young adult B-cell ALL (below 25 years)
  • Below 50 kg: 0.2-5 x 10^6 CAR-positive viable T cells/kg
  • Above 50 kg: 0.1-2.5 x 10^8 CAR-positive viable T cells/kg
• Injection, suspension for adult relapsed or refractory diffuse large B-cell lymphoma
  • 0.6-6 x 10^8 CAR-positive viable T cells

Acute Lymphoblastic Leukemia

Adult and pediatric dosage

Lymphodepleting chemotherapy

• Fludarabine 30 mg/m2 intravenous once a day for 4 days PLUS  
• Cyclophosphamide 500 mg/m2 intravenous once a day for 2 days starting with the first dose of fludarabine.

Tisagenlecleucel Intravenous infusion

• Administer 2-14 days after completing lymphodepleting chemotherapy.
• Premedicate with acetaminophen and diphenhydramine (see Administration)
  • Below 50 kg: 0.2-5 x 106 CAR-positive viable T cells/kg
  • Above 50 kg: 0.1-2.5 x 108 CAR-positive viable T cells/kg
• Infuse autologously prepared, weight-based intravenous for individual patients at 10-20 mL/min
• Do not use a leukocyte-depleting filter.
• Adjust infusion rate as appropriate for smaller children and smaller volumes.
• Also see Administration.

Large B-Cell Lymphoma

Adult dosage

Lymphodepleting chemotherapy

• Lymphodepleting chemotherapy may be omitted if WBC counts is below 1 x 109/L within 1 week before tisagenlecleucel infusion.
• Fludarabine 25 mg/m2 intravenous once a day for 3 days PLUS
• Cyclophosphamide 250 mg/m2 intravenous once a day for 3 days starting with the first dose of fludarabine

Alternate lymphodepleting chemotherapy

• Bendamustine 90 mg/m2 intravenous once a day for 2 days if a patient experienced a previous Grade 4 hemorrhagic cystitis with cyclophosphamide or demonstrates resistance to a previous cyclophosphamide-containing regimen.

Tisagenlecleucel IV infusion

• Administer 2-11 days after completing lymphodepleting chemotherapy.
• Premedicate with acetaminophen and diphenhydramine (see Administration)
• 0.6-6 x 108 CAR-positive viable T cells/kg

Follicular Lymphoma

Adult dosage

Lymphodepleting chemotherapy

• Lymphodepleting chemotherapy may be omitted if WBC count is below 1 x 109/L within 1 week before tisagenlecleucel infusion
• Fludarabine 25 mg/m2 intravenous once a day for 3 days PLUS
• Cyclophosphamide 250 mg/m2 intravenous once a day for 3 days starting with the first dose of fludarabine

Alternate lymphodepleting chemotherapy

• Bendamustine 90 mg/m2 intravenous once a day for 2 days if a patient experienced a previous Grade 4 hemorrhagic cystitis with cyclophosphamide or demonstrates resistance to a previous cyclophosphamide-containing regimen.

Tisagenlecleucel IV infusion

• Administer 2-6 days after completing lymphodepleting chemotherapy.
• Premedicate with acetaminophen and diphenhydramine (see Administration)
• 0.6-6 x 108 CAR-positive viable T cells/kg

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Tisagenlecleucel has severe interactions with no other drugs.
• Tisagenlecleucel has serious interactions with at least 203 other drugs.
• Tisagenlecleucel has moderate interactions with no other drugs.
• Tisagenlecleucel has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Tisagenlecleucel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Tisagenlecleucel?”

Cautions

• Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment in a majority of patients (see Black Box Warnings and Adverse Effects)
• Neurological toxicities, which may be severe or life-threatening, can occur following treatment (see Black Box Warnings)
• Available only through a restricted access program (see Black Box Warnings)
• Allergic reactions may occur during infusion; serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) or dextran 40 in the product
• Serious infections, including life-threatening or fatal infections, reported; before administering, infection prophylaxis for neutropenia should follow local guidelines; monitor for signs and symptoms of infection after treatment and treat appropriately
• Viral reactivation can occur; hepatitis B virus (HBV) reactivation can result in fulminant hepatitis, hepatic failure, and death; perform screening for HBV, and hepatitis C virus (HCbyordance with clinical guidelines before collection of cells for manufacturing
• Prolonged cytopenias may occur and last for several weeks following lymphodepleting chemotherapy and tisagenlecleucel; prolonged neutropenia has been associated with increased risk of infection; myeloid growth factors, particularly GM-CSF, are not recommended during the first 3 weeks after tisagenlecleucel infusion or until CRS has resolved
• Hypogammaglobulinemia and agammaglobulinemia (IgG) can occur in patients with a complete remission (CR); monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement standard guidelines
• Secondary malignancies or recurrence of leukemia may occur; monitor the patient life-long for secondary malignancies.
• Owing to the potential for neurological events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following treatment; advise patients to refrain from driving and engaging in hazardous occupations or activities
• HIV and the lentivirus used to make tisagenlecleucel have limited, short spans of identical genetic material (RNA); therefore, some commercial HIV nucleic acid test (NAT) tests may yield false-positive results in patients who have received tisagenlecleucel
• Hemophagocytic lymph histiocytosis (HLH)/macrophage activation syndrome (MAS), which can be life-threatening or fatal, has occurred; all HLH events occurred during ongoing CRS and resolved; treat HLH as per institutional standards.
• Immunization with live viral vaccines
  • The safety of immunization with live viral vaccines during or following treatment has not been studied.
  • Vaccination with live-virus vaccines is not recommended for at least 2 weeks before the start of lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterward.

Pregnancy and Lactation

• Data are not available in pregnant women; not recommended for women who are pregnant, and discuss with the treating physician about pregnancy after administration; report pregnancies to Novartis Pharmaceuticals Corporation at 1-888-669-6682
• No animal reproductive and developmental toxicity studies have been conducted.
• Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia
• Pregnant women who have received tisagenlecleucel may have hypogammaglobulinemia; assess immunoglobulin levels in newborns of treated mothers.
• Pregnancy status of females with reproductive potential should be verified; sexually active females of reproductive potential should have a pregnancy test before starting treatment.
• Contraception: See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy; limited exposure data available concerning the duration of contraception following treatment with tisagenlecleucel
• Lactation
  • Unknown if distributed in human breast milk.
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition.