tisagenlecleucel (Rx)

Brand and Other Names:Kymriah
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

Single-dose units contain specific amounts of T-cell depending on the patient’s body weight that are suspended in a patient-specific infusion bag

See the certificate of analysis (CoA) for actual cell count following individual preparation

injection, suspension for pediatric and young adult B-cell ALL (<25 years)

  • ≤50 kg: 0.2-5 x 10^6 CAR-positive viable T cells/kg
  • >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

CD19-directed genetically modified autologous T-cell immunotherapy indicated for young adults aged <25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse

One treatment course consists of fludarabine and cyclophosphamide lymphodepleting chemotherapy followed by IV infusion of tisagenlecleucel

Lymphodepleting chemotherapy

  • Fludarabine 30 mg/m² IV qDay for 4 days PLUS
  • Cyclophosphamide 500 mg/m² IV qDay for 2 days starting with the first dose of fludarabine

Tisagenlecleucel IV infusion

  • Administer 2-14 days after completing lymphodepleting chemotherapy
  • Premedicate with acetaminophen and diphenhydramine (see Administration)
  • ≤50 kg: 0.2-5 x 10^6 CAR-positive viable T cells/kg
  • >50 kg: 0.1-2.5 x 10^8 CAR-positive viable T cells/kg
  • Infuse autologously prepared, weight-based IV for individual patient 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

Indicated for adults with relapsed or refractory large B-cell lymphoma (r/rDLBCL) after ≥2 lines of systemic therapy including DLBCL not otherwise specified, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma

One treatment course consists of fludarabine and cyclophosphamide lymphodepleting chemotherapy followed by IV infusion of tisagenlecleucel

Lymphodepleting chemotherapy

  • Lymphodepleting chemotherapy may be omitted if WBC count ≤1 x 10^9/L within 1 week before tisagenlecleucel infusion
  • Fludarabine 25 mg/m² IV qDay for 3 days PLUS
  • Cyclophosphamide 250 mg/m² IV qDay for 3 days starting with the first dose of fludarabine
  • Alternate lymphodepleting chemotherapy
    • Bendamustine 90 mg/m² IV qDay 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 10^8 CAR-positive viable T cells/kg
  • Also see Administration

Dosage Modifications

Cytokine release syndrome (CRS) management

  • Prodromal syndrome
    • Symptoms: Low-grade fever, fatigue, anorexia
    • Observe in person; exclude infection; administer antibiotics per local guidelines if neutropenic; provide symptomatic support
  • CRS requiring mild intervention
    • 1 or more symptoms of the following: High fever, hypoxia, mild hypotension
    • Administer antipyretics, oxygen, IV fluids, and/or low-dose vasopressors as needed
  • CRS requiring moderate to aggressive intervention
    • 1 or more symptoms of the following: Hemodynamic instability despite IV fluids and vasopressor support, and/or worsening respiratory distress (including pulmonary infiltrates, increasing oxygen requirement including high-flow oxygen, and/or need for mechanical ventilation), and/or rapid clinical deterioration
    • Administer high-dose or multiple vasopressors, oxygen, mechanical ventilation, and/or other supportive care as needed
    • Administer tocilizumab, weight <30 kg: 12 mg/kg IV infused over 1 hr
    • Administer tocilizumab, weight ≥30 kg: 8 mg/kg IV infused over 1 hr; not to exceed 800 mg/dose
    • Repeat tocilizumab as needed at a minimum interval of 8 hr if there is no clinical improvement
    • If no response to second dose of tocilizumab, consider a third dose or pursue alternative measures for CRS treatment
    • Not to exceed a total of 4 tocilizumab doses
    • If no clinical improvement within 12-18 hr after the first tocilizumab dose, or worsening at any time, administer methylprednisolone 2 mg/kg as an initial dose, then 2 mg/kg/day until vasopressors and high flow oxygen are no longer needed, then taper methylprednisolone

Dosing Considerations

For autologous use only

Adult relapsed or refractory DLBCL

  • Limitation of use: Not indicated for treatment of patients with primary central nervous system lymphoma

Dosage Forms & Strengths

injection, suspension for pediatric and young adult B-cell ALL (<25 years)

  • Single-dose units contain specific amounts of T-cell depending on the patient’s body weight that are suspended in a patient-specific infusion bag
  • ≤50 kg: 0.2-5 x 10^6 CAR-positive viable T cells/kg
  • >50 kg: 0.1-2.5 x 10^8 CAR-positive viable T cells/kg
  • See the certificate of analysis (CoA) for actual cell count following individual preparation

Acute Lymphoblastic Leukemia

CD19-directed genetically modified autologous T-cell immunotherapy indicated for patients aged <25 years with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse

One treatment course consists of fludarabine and cyclophosphamide lymphodepleting chemotherapy followed by IV infusion of tisagenlecleucel

Lymphodepleting chemotherapy

  • Fludarabine 30 mg/m² IV qDay for 4 days PLUS
  • Cyclophosphamide 500 mg/m² IV qDay for 2 days starting with the first dose of fludarabine

Tisagenlecleucel IV infusion

  • Administer 2-14 days after completing lymphodepleting chemotherapy
  • Premedicate with acetaminophen and diphenhydramine (see Administration)
  • ≤50 kg: 0.2-5 x 10^6 CAR-positive viable T cells/kg
  • >50 kg: 0.1-2.5 x 10^8 CAR-positive viable T cells/kg
  • Infuse autologously prepared, weight-based IV for individual patient 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

Dosage Modifications

Cytokine release syndrome (CRS) management

  • Prodromal syndrome
    • Symptoms: Low-grade fever, fatigue, anorexia
    • Observe in person; exclude infection; administer antibiotics per local guidelines if neutropenic; provide symptomatic support
  • CRS requiring mild intervention
    • 1 or more symptoms of the following: High fever, hypoxia, mild hypotension
    • Administer antipyretics, oxygen, IV fluids, and/or low-dose vasopressors as needed
  • CRS requiring moderate to aggressive intervention
    • 1 or more symptoms of the following: Hemodynamic instability despite IV fluids and vasopressor support, and/or worsening respiratory distress (including pulmonary infiltrates, increasing oxygen requirement including high-flow oxygen, and/or need for mechanical ventilation), and/or rapid clinical deterioration
    • Administer high-dose or multiple vasopressors, oxygen, mechanical ventilation, and/or other supportive care as needed
    • Administer tocilizumab, weight <30 kg: 12 mg/kg IV infused over 1 hr
    • Administer tocilizumab, weight ≥30 kg: 8 mg/kg IV infused over 1 hr; not to exceed 800 mg/dose
    • Repeat tocilizumab as needed at a minimum interval of 8 hr if there is no clinical improvement
    • If no response to second dose of tocilizumab, consider a third dose or pursue alternative measures for CRS treatment
    • Not to exceed a total of 4 tocilizumab doses
    • If no clinical improvement within 12-18 hr after the first tocilizumab dose, or worsening at any time, administer methylprednisolone 2 mg/kg as an initial dose, then 2 mg/kg/day until vasopressors and high flow oxygen are no longer needed, then taper methylprednisolone

Dosing Considerations

For autologous use only

Next:

Interactions

Interaction Checker

and tisagenlecleucel

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (23)

              • adenovirus types 4 and 7 live, oral

                tisagenlecleucel decreases effects of adenovirus types 4 and 7 live, oral by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • betamethasone

                betamethasone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • corticotropin

                corticotropin decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • cortisone

                cortisone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • deflazacort

                deflazacort decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • dexamethasone

                dexamethasone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • filgrastim

                tisagenlecleucel, filgrastim. Other (see comment). Avoid or Use Alternate Drug. Comment: Prolonged cytopenias occur following lymphodepleting chemotherapy and tisagenlecleucel infusion. Myeloid growth factors are not recommended during the first 3 weeks after tisagenlecleucel infusion or until cytokine release syndrome has resolved.

              • fludrocortisone

                fludrocortisone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • hydrocortisone

                hydrocortisone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • measles mumps and rubella vaccine, live

                tisagenlecleucel decreases effects of measles mumps and rubella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • measles, mumps, rubella and varicella vaccine, live

                tisagenlecleucel decreases effects of measles, mumps, rubella and varicella vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • methylprednisolone

                methylprednisolone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • palifermin

                palifermin increases toxicity of tisagenlecleucel by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

              • pegfilgrastim

                tisagenlecleucel, pegfilgrastim. Other (see comment). Avoid or Use Alternate Drug. Comment: Prolonged cytopenias occur following lymphodepleting chemotherapy and tisagenlecleucel infusion. Myeloid growth factors are not recommended during the first 3 weeks after tisagenlecleucel infusion or until cytokine release syndrome has resolved.

              • prednisolone

                prednisolone decreases effects of tisagenlecleucel by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • prednisone

                prednisone decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • rotavirus oral vaccine, live

                tisagenlecleucel decreases effects of rotavirus oral vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • sargramostim

                tisagenlecleucel, sargramostim. Other (see comment). Avoid or Use Alternate Drug. Comment: Prolonged cytopenias occur following lymphodepleting chemotherapy and tisagenlecleucel infusion. Myeloid growth factors are not recommended during the first 3 weeks after tisagenlecleucel infusion or until cytokine release syndrome has resolved.

              • smallpox (vaccinia) vaccine, live

                tisagenlecleucel decreases effects of smallpox (vaccinia) vaccine, live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • triamcinolone acetonide injectable suspension

                triamcinolone acetonide injectable suspension decreases effects of tisagenlecleucel by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid using corticosteroids as premedication or during treatment with tisagenlecleucel, except for life-threatening emergence (eg, cytokine release syndrome).

              • varicella virus vaccine live

                tisagenlecleucel decreases effects of varicella virus vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • yellow fever vaccine

                tisagenlecleucel decreases effects of yellow fever vaccine by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              • zoster vaccine live

                tisagenlecleucel decreases effects of zoster vaccine live by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Vaccination with live-virus vaccines is not recommended for at least 2 weeks before starting lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards.

              Monitor Closely (1)

              • zoster vaccine recombinant

                tisagenlecleucel decreases effects of zoster vaccine recombinant by pharmacodynamic antagonism. Use Caution/Monitor. Immunosuppressive therapies may reduce the effectiveness of zoster vaccine recombinant.

              Minor (0)

                Previous
                Next:

                Adverse Effects

                Percentages include all grades unless otherwise noted

                >10% (Pediatric & Young Adults with ALL)

                Cytokine release syndrome (79%)

                Cytokine release syndrome, grades 3-4 (49%)

                Hypogammaglobulinemia (43%)

                Infection, unspecified pathogen (41%)

                Pyrexia (40%)

                Prolonged neutropenia, Day 28 (40%)

                Febrile neutropenia, grades 3-4 (37%)

                Decreased appetite (37%)

                Headache (37%)

                Encephalopathy (34%)

                Hypotension (31%)

                Increased AST, grades 3-4 (28%)

                Hypokalemia, grades 3-4 (27%)

                Prolonged thrombocytopenia, Day 28 (27%)

                Viral infection (26%)

                Tachycardia (26%)

                Nausea (26%)

                Diarrhea (26%)

                Vomiting (26%)

                Fatigue (25%)

                Hypoxia (24%)

                Acute kidney injury (24%)

                Hypotension, grades 3-4 (22%)

                Edema (21%)

                Cough (21%)

                Increased ALT, grades 3-4 (21%)

                Increased bilirubin, grades 3-4 (21%)

                Delirium (21%)

                Hypophosphatemia, grades 3-4 (19%)

                Hypertension (19%)

                Bacterial infection (19%)

                Constipation (18%)

                Viral infection, grades 3-4 (18%)

                Hypoxia, grades 3-4 (18%)

                Pain (18%)

                Prolonged neutropenia, Day 56 (17%)

                Infection, unspecified pathogen, grades 3-4 (16%)

                Hypofibrinogenemia with grades 3-4 CRS (16%)

                Abdominal pain (16%)

                Pain in extremity (16%)

                Pulmonary edema (16%)

                Rash (16%)

                Decreased appetite, grades 3-4 (15%)

                Pyrexia, grades 3-4 (15%)

                Myalgia (15%)

                Fungal infection (13%)

                Anxiety (13%)

                Bacterial infection, grades 3-4 (13%)

                Acute kidney injury, grades 3-4 (13%)

                Increased INR (13%)

                Dyspnea, grades 3-4 (12%)

                Prolonged thrombocytopenia, Day 56 (12%)

                Arthralgia (12%)

                Tachypnea (12%)

                >10% (Adults with DLBCL)

                Lymphopenia, grades 3-4 (97%)

                Neutropenia, grades 3-4 (81%)

                Leukopenia, grades 3-4 (77%)

                Cytokine release syndrome (74%)

                Anemia, grades 3-4 (58%)

                Thrombocytopenia, grades 3-4 (54%)

                Infection, unspecified pathogen (42%)

                Pyrexia (34%)

                Diarrhea (31%)

                Nausea (27%)

                Fatigue (26%)

                Hypotension (26%)

                Infection, unspecified pathogen grades 3-4 (25%)

                Hypophosphatemia (24%)

                Cytokine release syndrome, grades 3-4 (23%)

                Edema (23%)

                Headache (21%)

                Cough (19%)

                Dyspnea (18%)

                Febrile neutropenia, grades 3-4 (17%)

                Acute kidney injury (17%)

                Constipation (16%)

                Encephalopathy (16%)

                Pain (15%)

                Hypogammaglobulinemia (14%)

                Tachycardia (13%)

                Chills (13%)

                Decreased appetite (12%)

                Hypokalemia (12%)

                Hyponatremia (11%)

                Decreased weight (11%)

                Dizziness (11%)

                Encephalopathy, grades 3-4 (11%)

                1-10% (Pediatric & Young Adults with ALL)

                Sleep disorders (10%)

                Face edema (10%)

                Peripheral edema, grades 3-4 (10%)

                Chills (10%)

                Fluid overload (10%)

                Back pain (10%)

                Pleural effusion (10%)

                Nasal congestion (10%)

                Pulmonary edema, grades 3-4 (10%)

                Encephalopathy, grades 3-4 (10%)

                Fungal infection, grades 3-4 (7%)

                Blood and lymphatic system disorders: DIC (9%)

                Histiocytosis lymphocytic hemophagocytosis (7%)

                Coagulopathy (6%)

                Blood creatinine increased (7%)

                aPTT prolonged (6%)

                Respiratory, thoracic, and mediastinal disorders: Respiratory distress (6%), respiratory failure (6%), acute RDS (4%)

                Cardiac disorders: Cardiac arrest (4%), cardiac failure (7%)

                Metabolism and nutrition disorders: Tumor lysis syndrome (6%)

                Vascular disorders: Capillary leak syndrome (3%)

                General disorders and administration site conditions: Multiple organ dysfunction syndrome (3%)

                Nervous System: Intracranial hemorrhage (1%), seizure (3%)

                Gastrointestinal disorders: Abdominal compartment syndrome (1%)

                Immune system disorders: GVHD (1%)

                1-10% (Adults with DLBCL)

                Arthralgia (10%)

                Hypotension, grades 3-4 (8%)

                Fatigue, grades 3-4 (7%)

                Pyrexia, grades 3-4 (6%)

                Acute kidney injury, grades 3-4 (6%)

                Dyspnea, grades 3-4 (6%)

                Hypogammaglobulinemia, grades 3-4 (4%)

                Appetite decreased, grades 3-4 (4%)

                Tachycardia, grades 3-4 (3%)

                Pain, grades 3-4 (3%)

                Weight decreased, grades 3-4 (3%)

                Edema, grades 3-4 (2%)

                Diarrhea, grades 3-4 (1%)

                Nausea, grades 3-4 (1%)

                Constipation, grades 3-4 (1%)

                Dizziness, grades 3-4 (1%)

                Previous
                Next:

                Warnings

                Black Box Warnings

                Cytokine release syndrome

                • Cytokine release syndrome (CRS), including fatal or life-threatening reactions, reported in a majority of patients (see Adverse Effects)
                • Median time to CRS onset was 3 days (range: 1-22 days)
                • Key manifestations of CRS include high fever, lower than normal blood pressure, and difficulty breathing, and may be associated with hepatic, renal, and cardiac dysfunction and coagulopathy
                • Risk factors for severe CRS are high preinfusion tumor burden (>50% blasts in bone marrow), uncontrolled or accelerating tumor burden following lymphodepleting chemotherapy, active infections, and/or inflammatory processes
                • Do not administer to patients with active infection or inflammatory disorders
                • Delay tisagenlecleucel administration after lymphodepleting chemotherapy if patient has unresolved serious adverse reactions from preceding chemotherapies (including pulmonary toxicity, cardiac toxicity, or hypotension), active uncontrolled infection, active graft versus host disease (GVHD), or worsening of leukemia burden
                • Treat severe or life-threatening CRS with tocilizumab
                  • Ensure that 2 doses of tocilizumab are available on site prior to tisagenlecleucel administration
                  • Monitor for CRS signs or symptoms for at least 4 weeks after treatment
                  • Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time
                  • At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care, tocilizumab, and/or corticosteroids as indicated

                Neurological toxicities

                • Neurological toxicities, which may be severe or life-threatening, can occur following treatment, including concurrently with CRS
                • The majority of neurological toxicities occurred within 8 weeks after treatment
                • The most common neurological toxicities were headache, encephalopathy, delirium, anxiety, and tremor (also see Adverse Effects)
                • Other manifestations of neurological toxicities included disturbances in consciousness, disorientation, confusion, agitation, seizures, mutism, and aphasia
                • Monitor for neurological events after treatment; provide supportive care as needed

                Restricted access program

                • Available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYMRIAH REMS
                • Further information is available at www.kymriah-rems.com or 1-844-4KYMRIAH
                • REMS requirements
                  • Healthcare facilities that dispense and administer tisagenlecleucel must be enrolled and comply with the REMS requirements
                  • Certified healthcare facilities must have onsite, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each patient for administration within 2 hr after tisagenlecleucel IV infusion, if needed for treatment of CRS
                  • Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer tisagenlecleucel are trained about the management of CRS and neurological toxicities

                Contraindications

                None

                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, hepatitis C virus (HCV), and HIV in accordance 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 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

                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 prior to the start of lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery afterwards
                Previous
                Next:

                Pregnancy

                Pregnancy

                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 prior to starting treatment

                Contraception: See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the 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 from the underlying maternal condition

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

                Previous
                Next:

                Pharmacology

                Mechanism of Action

                CD19-directed genetically modified autologous T-cell immunotherapy that involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells

                CAR is composed of a murine single-chain antibody fragment that recognizes CD19 and is fused to intracellular signaling domains from 4-1BB (CD137) and CD3 zeta

                CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances expansion and persistence of tisagenlecleucel

                CAR transmits a signal to promote T-cell expansion owing to binding of CD19 expressed cells, activation, target cell elimination, and persistence of tisagenlecleucel cells

                Absorption

                Peak plasma concentration: 34,700 copies/mcg (responsive patients); 20,000 copies/mcg (nonresponsive [NR] patients)

                Peak plasma time: 9.91 days (responsive patients); 20 days (NR patients)

                AUC: 318,000 copies/mcg·day (responsive patients); 156,000 (NR patients)

                Peak plasma concentration and AUC were ~2-fold higher in CR/CRi patients compared with NR patients

                Distribution

                Tisagenlecleucel was present in blood as well as bone marrow and was measurable beyond 2 yr

                Blood to bone marrow partitioning suggested that tisagenlecleucel distribution in bone marrow was 44% of that present in blood at day 28, while at months 3 and 6 tisagenlecleucel distributed at 67% and 69%, respectively, indicating high distribution to bone marrow

                Elimination

                Half-life: 16.8 days (responsive patients); 2.52 days (NR patients)

                Previous
                Next:

                Administration

                IV Preparation

                Confirm infusion time in advance, and adjust start time for thaw so that tisagenlecleucel is available for infusion when recipient is ready

                Ensure 2 doses of tocilizumab and emergency equipment are available prior to infusion and during the recovery period; premedicate patient; see Dosing

                Confirm patient identity prior to preparation, match the patient's identity with the patient identifiers on the tisagenlecleucel infusion bag; tisagenlecleucel is for autologous use only

                Inspect the infusion bag for any breaks or cracks before thawing; if bag is compromised, do not infuse the contents; contact Novartis at 1-844-4KYMRIAH

                Place infusion bag inside a second, sterile bag in case of a leak and to protect ports from contamination; thaw infusion bag at 37°C using either a water bath or dry thaw method until there is no visible ice in the infusion bag

                Remove bag from thawing device immediately; do not store product bag at 37°C

                Once thawed, stored at room temperature (20-25°C) for up to 30 minutes

                Do not wash, spin down, and/or resuspend tisagenlecleucel in new media prior to infusion; inspect contents of the thawed infusion bag for any visible cell clump; if visible cell clumps remain, gently mix the contents of the bag; small clumps of cellular material should disperse with gentle manual mixing

                Do not infuse tisagenlecleucel if clumps are not dispersed, the infusion bag is damaged or leaking, or otherwise appears to be compromised; if this occurs, contact Novartis at 1-844-4KYMRIAH

                IV Administration

                Premedication

                • Premedicate with acetaminophen and diphenhydramine or another H1-antihistamine ~30-60 minutes before tisagenlecleucel infusion
                • Do not use corticosteroids at any time except in the case of a life-threatening emergency

                Tisagenlecleucel infusion

                • Administer IV infusion at 10-20 mL/min, adjusted as appropriate for smaller children and smaller volume
                • Infusion bag volume ranges from 10-50 mL
                • Do not use a leukocyte-depleting filter; prime tubing prior to infusion with 0.9% NaCl
                • Infuse all contents of the infusion bag; rinse infusion bag with 10-30 mL 0.9% NaCl while maintaining a closed tubing system to assure as many cells as possible are infused into the patient
                • Follow local biosafety guidelines applicable for handling and disposal of such products

                Storage

                Frozen product

                • Store infusion bag in the vapor phase of liquid nitrogen ≤-148°F (≤-120°C) in a temperature-monitored system
                • Use closed, break-proof, leak-proof containers when transporting infusion bags within the facility

                Thawed infusion bag

                • Stored at room temperature 68-77°F (20-25°C) for up to 30 minutes
                Previous
                Next:

                Images

                No images available for this drug.
                Previous
                Next:

                Patient Handout

                A Patient Handout is not currently available for this monograph.
                Previous
                Next:

                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
                Email to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Email Forms to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Previous
                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.