Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving tisagenlecleucel. Do not administer tisagenlecleucel to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurological toxicities, which may be severe or life-threatening, can occur following treatment with tisagenlecleucel, including concurrently with CRS. Monitor for neurological events after treatment with tisagenlecleucel. Provide supportive care as needed.
Tisagenlecleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYMRIAH REMS.
For autologous use only; confirm patient identity prior to prescribing. A single dose may be contained in 1 to 3 patient-specific infusion bags; verify the number of bags received for the dose with the certificate of conformance/analysis (cells from all bags must be infused to complete a single dose). The actual number of chimeric antigen receptor (CAR)–positive T cells in tisagenlecleucel are provided in the certificate of analysis. Begin infection prophylaxis (according to local recommendations) prior to initiating tisagenlecleucel. Do not administer tisagenlecleucel to patients with active infection or inflammatory disorders. Delay tisagenlecleucel infusion for unresolved serious adverse reactions from chemotherapy (eg, pulmonary/cardiac reactions, hypotension), or active uncontrolled infection, active graft versus host disease (GVHD), or worsening leukemia burden following lymphodepleting chemotherapy. Ensure that tocilizumab is available (a minimum of 2 doses) on site prior to tisagenlecleucel infusion. Myeloid growth factors, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF) (sargramostim), are not recommended during the first 3 weeks after tisagenlecleucel infusion.
Premedications: Premedicate with acetaminophen and diphenhydramine (or another H1-antihistamine) ~30 to 60 minutes prior to tisagenlecleucel infusion. Avoid prophylactic use of corticosteroids (may interfere with tisagenlecleucel activity).
Acute lymphoblastic leukemia (relapsed or refractory): Tisagenlecleucel is administered 2 to 14 days after completion of a lymphodepleting chemotherapy course of fludarabine and cyclophosphamide. Note: Delay tisagenlecleucel infusion for unresolved serious adverse reactions from chemotherapy (eg, pulmonary/cardiac reactions or hypotension), active uncontrolled infection, active GVHD, or increasing leukemia burden following lymphodepleting chemotherapy.
Children and Adolescents weighing ≤50 kg: IV: 0.2 to 5 x 106 CAR-positive viable T cells per kg body weight.
Children and Adolescents weighing >50 kg: IV: 0.1 to 2.5 x 108 CAR-positive viable T cells.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Note: Evaluate patients immediately at the first sign of cytokine release syndrome (CRS). Myeloid growth factors, particularly GM-CSF (sargramostim), are not recommended during the first 3 weeks after tisagenlecleucel infusion or until CRS has resolved.
Children and Adolescents:
Cytokine release syndrome (CRS):
Prodromal syndrome (low-grade fever, fatigue, anorexia): Observe in person, exclude infection, administer antibiotics (per local guidelines) if neutropenic, manage symptomatically.
CRS requiring mild intervention (one or more of the following: High fever, hypoxia, and/or mild hypotension): Administer antipyretics, oxygen, IV fluids, and/or low-dose vasopressors as needed.
CRS requiring moderate to aggressive intervention (one or more of the following: Hemodynamic instability despite IV fluids and vasopressor support, worsening respiratory distress [including pulmonary infiltrates and increasing oxygen requirement including high-flow oxygen and/or need for mechanical ventilation], rapid clinical deterioration): Administer high-dose or multiple vasopressors, oxygen, mechanical ventilation, and/or other supportive care as needed. Administer IV tocilizumab over 1 hour (weight-dependent dosing: If weight <30 kg: Tocilizumab 12 mg/kg; if weight ≥30 kg: Tocilizumab 8 mg/kg; maximum tocilizumab dose: 800 mg/dose; see tocilizumab monograph). If no clinical improvement, repeat tocilizumab as needed with at least an 8-hour interval between consecutive doses; if no response to the second tocilizumab dose consider a third tocilizumab dose or pursue alternative CRS management. Limit tocilizumab to a maximum of 4 doses. If no clinical improvement within 12 to 18 hours of the first tocilizumab dose or worsening at any time, administer methylprednisolone 2 mg/kg initially, then 2 mg/kg/day until vasopressors and high-flow oxygen are no longer needed, then taper corticosteroids.
Other adverse reactions:
Hypogammaglobulinemia: Manage with IV immune globulin replacement and with infection precautions and antibiotic and/or antiviral prophylaxis as indicated.
Neurologic toxicity: Exclude other causes and manage with supportive care as clinically indicated.
Neutropenic fever: Evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as clinically indicated.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Tisagenlecleucel: Drug information")
Note: For autologous use only; confirm patient identity on each bag prior to infusion. A single dose may be contained in 1 to 3 patient-specific infusion bags; verify the number of bags received for the dose with the certificate of conformance/analysis (cells from all bags must be infused to complete a single dose). The actual number of CAR-positive T cells in tisagenlecleucel are provided in the certificate of analysis. Begin infection prophylaxis (according to local recommendations) prior to initiating tisagenlecleucel. Do not administer tisagenlecleucel to patients with active infection or inflammatory disorders. Delay tisagenlecleucel infusion for unresolved serious adverse reactions from chemotherapy (eg, pulmonary/cardiac reactions or hypotension), or active uncontrolled infection, active graft versus host disease (GVHD), or worsening leukemia burden following lymphodepleting chemotherapy. Ensure that tocilizumab is available (a minimum of 2 doses) on site prior to tisagenlecleucel infusion. Myeloid growth factors, particularly GM-CSF (sargramostim), are not recommended during the first 3 weeks after tisagenlecleucel infusion.
Premedications: Premedicate with acetaminophen and diphenhydramine (or another H1-antihistamine) ~30 to 60 minutes prior to tisagenlecleucel infusion. Avoid prophylactic use of corticosteroids (may interfere with tisagenlecleucel activity).
Acute lymphoblastic leukemia, relapsed or refractory: Note: A treatment course consists of lymphodepleting chemotherapy (with fludarabine and cyclophosphamide) followed by tisagenlecleucel 2 to 14 days following completion of the fludarabine/cyclophosphamide regimen. Dosing is based on weight reported at the time of leukapheresis.
<25 years and ≤50 kg: IV: 0.2 to 5 × 106 CAR-positive viable T cells per kg body weight.
<25 years and >50 kg: IV: 0.1 to 2.5 × 108 CAR-positive viable T cells.
Diffuse large B-cell lymphoma, relapsed or refractory: IV: 0.6 to 6 × 108 CAR-positive viable T cells. A treatment course consists of lymphodepleting chemotherapy (with fludarabine and cyclophosphamide or with bendamustine for cyclophosphamide intolerance or resistance to a previous cyclophosphamide-containing regimen) followed by tisagenlecleucel 2 to 11 days following completion of the lymphodepleting regimen; lymphodepleting chemotherapy may be omitted if the patient is experiencing significant cytopenia (eg, if the WBC ≤1,000/mm3) within 1 week prior to tisagenlecleucel infusion.
Follicular lymphoma, relapsed or refractory: IV: 0.6 to 6 × 108 CAR-positive viable T cells. A treatment course consists of lymphodepleting chemotherapy (with fludarabine and cyclophosphamide or with bendamustine for cyclophosphamide intolerance or resistance to a previous cyclophosphamide-containing regimen) followed by tisagenlecleucel 2 to 6 days following completion of the lymphodepleting regimen; lymphodepleting chemotherapy may be omitted if the patient is experiencing significant cytopenia (eg, if the WBC ≤1,000/mm3) within 1 week prior to tisagenlecleucel infusion.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Kymriah: (1 ea) [contains albumin human, dextran 40, dimethyl sulfoxide]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intravenous:
Kymriah: 600000000 CELLS (1 ea) [contains albumin human, dextran 40, dimethyl sulfoxide]
For autologous use only; confirm patient identity prior to infusion.
For IV use only. Coordinate the timing of administration with thawing (may only be stored for up to 30 minutes at room temperature); infusion start time may need to be adjusted based on thawing.
Prior to administration: Confirm patient identity and match to patient identifiers on the infusion bag (preceded by the letters "DIN" or "Aph ID"; see manufacturer's labeling). Ensure tocilizumab (at least 2 doses) and emergency equipment are available prior to infusion and during recovery period. Premedicate with acetaminophen and diphenhydramine (or other H1-antihistamine) ~30 to 60 minutes prior to tisagenlecleucel infusion. Do not use corticosteroids at any time (may interfere with tisagenlecleucel activity) except in the case of life-threatening emergency.
Inspect the contents of the thawed infusion bag for visible cell clumps; 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 if clumps are not dispersed, the infusion bag is damaged or leaking, or it otherwise appears to be compromised. Apply universal precautions for product handling.
Administration: Prime the tubing with NS prior to infusion. Infuse at a rate of 10 to 20 mL/minute, adjusting as appropriate for smaller children and smaller infusion volumes. Infuse entire contents of bag (infusion bag volume ranges from 10 to 50 mL), then (while maintaining a closed tubing system) rinse infusion bag with 10 to 30 mL NS to assure as many cells as possible are infused. Do not use a lymphocyte depleting filter.
IV: For IV use only. Coordinate the timing of administration with thawing (once thawed and at room temperature, infuse within 30 minutes); infusion start time may need to be adjusted based on thawing.
Prime the tubing with NS prior to infusion. Infuse at a rate of 10 to 20 mL/minute, adjusting as appropriate for smaller volumes. Infuse entire contents of bag (infusion bag volume ranges from 10 to 50 mL), then (while maintaining a closed tubing system) rinse infusion bag with 10 to 30 mL NS to assure as many cells as possible are infused. Do not use a lymphocyte depleting filter. If more than 1 bag is being administered, thaw 1 bag at a time, wait to thaw/infuse the next bag until it is determined that the previous bag is safely administered. Cells from all bags must be infused to complete a single dose.
Prior to administration: Ensure tocilizumab and emergency equipment are available prior to infusion and during recovery period. Premedicate with acetaminophen and diphenhydramine (or other histamine-1 antihistamine) ~30 to 60 minutes prior to tisagenlecleucel infusion. Avoid prophylactic use of corticosteroids (may interfere with tisagenlecleucel activity). Confirm patient identity and match to patient identifiers (preceded by the letters "DIN" or "Aph ID") on the infusion bag. Inspect the contents of the thawed infusion bag(s) for visible cell clumps; 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 if clumps are not dispersed, if the infusion bag is damaged or leaking, or if it otherwise appears to be compromised. Apply universal precautions for product handling.
Store infusion bag(s) (frozen suspension) in a temperature-monitored system ≤−120°C (eg, in the vapor phase of liquid nitrogen). After thawing, may only be stored for up to 30 minutes at room temperature of 20°C to 25°C.
Treatment of B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse (FDA approved in pediatric patients [age not specified] and adults <25 years of age); treatment of 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, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (FDA approved in adults).
Kymriah may be confused with Kynamro.
Tisagenlecleucel may be confused with axicabtagene ciloleucel, betibeglogene autotemcel, brexucabtagene autoleucel, ciltacabtagene autoleucel, elivaldogene autotemcel, idecabtagene vicleucel, lisocabtagene maraleucel, sipuleucel-T.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are reported for both relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in pediatric patients and young adults and relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults unless otherwise indicated.
>10%:
Cardiovascular: Edema (including facial edema, fluid retention, and peripheral edema: 23% to 27%), hypertension (ALL: 19%; DLBCL: 4%), hypotension (including orthostatic hypotension: 25% to 29%), tachycardia (13% to 24%)
Dermatologic: Skin rash (11% to 18%)
Endocrine & metabolic: Hyperglycemia (ALL: grades 3/4: 13%), hypocalcemia (ALL: 20%; DLBCL: 5%), hypokalemia (grades 3/4: 13% to 28%), hypophosphatemia (grades 3/4: 20% to 24%), weight loss (ALL: 3%; DLBCL: 12%)
Gastrointestinal: Abdominal pain (10% to 18%), constipation (17% to 18%), decreased appetite (14% to 38%), diarrhea (29% to 31%; grades ≥3: 1%), nausea (27% to 29% grades ≥3: 1% to 3%), vomiting (ALL: 32%; grades ≥3: 1%; DLBCL: 9%)
Hematologic & oncologic: Anemia (ALL: 100%; DLBCL: grades 3/4: 59%), decreased serum fibrinogen (ALL: grades 3/4: 11%), febrile neutropenia (grades ≥3: 17% to 34%), hemorrhage (including anal hemorrhage, catheter site hemorrhage, cerebral hemorrhage, conjunctival hemorrhage, disseminated intravascular coagulation, gastrointestinal hemorrhage, hemarthrosis, hematuria, hemorrhagic cystitis, retinal hemorrhage, vaginal hemorrhage: 22% to 32%; grades ≥3: 8% to 10%), hypogammaglobulinemia (ALL: 53%; grades ≥3: 13%; DLBCL: 17%; grades ≥3: 6%), leukopenia (DLBCL: grades 3/4: 78%), lymphocytopenia (DLBCL: grades 3/4: 95%), neutropenia (ALL: 100%; DLBCL: grades 3/4: 82%), thrombocytopenia (ALL: 100%; DLBCL: grades 3/4: 56%)
Hepatic: Hyperbilirubinemia (ALL: grades 3/4: 19%), increased serum alanine aminotransferase (ALL: grades 3/4: 22%), increased serum aspartate aminotransferase (ALL: grades 3/4: 29%)
Hypersensitivity: Cytokine release syndrome (74% to 77%)
Infection: Bacterial infection (17% to 29%), fungal infection (11% to 15%), infection (48% to 57%), viral infection (ALL: 37%; DLBCL: 11%)
Nervous system: Anxiety (10% to 17%), chills (9% to 12%), delirium (ALL: 19%; DLBCL: 5%), dizziness (5% to 12%), encephalopathy (16% to 30%), fatigue (23% to 27%), headache (21% to 35%), pain (14% to 25%), peripheral neuropathy (4% to 12%), sleep disorder (10% to 11%)
Neuromuscular & skeletal: Arthralgia (14%), musculoskeletal pain (13% to 32%)
Renal: Acute kidney injury (including anuria, azotemia, renal tubular necrosis, increased serum creatinine: 17% to 22%)
Respiratory: Cough (17% to 27%), dyspnea (19% to 21%), hypoxia (ALL: 25%; DLBCL: 8%), nasal congestion (4% to 11%), pulmonary edema (ALL: 15%; DLBCL: 3%)
Miscellaneous: Fever (35% to 42%)
1% to 10%:
Cardiovascular: Capillary leak syndrome (1% to 3%), cardiac arrhythmia (including atrial fibrillation, supraventricular tachycardia, and ventricular premature contractions: 4% to 10%), flushing (ALL: 1%), heart failure (ALL: 9%; DLBCL: 1%), thrombosis (3% to 6%)
Dermatologic: Erythema of skin (2% to 6%), hyperhidrosis (4%), night sweats (ALL: 1%; DLBCL: 5%), pruritus (4% to 9%)
Endocrine & metabolic: Hypercalcemia (4%), increased serum iron (serum ferritin increased: 4% to 10%)
Gastrointestinal: Abdominal distention (4%), acute abdominal condition (abdominal compartment syndrome; ALL: 1%), stomatitis (4% to 6%), xerostomia (ALL: 1%; DLBCL: 5%)
Hematologic & oncologic: Decreased white blood cell count (B-cell aplasia: DLBCL: 1%), disorder of hemostatic components of blood (ALL: 6%), hemophagocytic lymphohistiocytosis (2% to 6%), increased fibrin degradation products (increased fibrin D dimer: 3% to 4%), pancytopenia (3% to 4%), prolonged prothrombin time (ALL: 4%), tumor lysis syndrome (2% to 6%)
Hepatic: Ascites (3% to 4%)
Hypersensitivity: Infusion-related reaction (3% to 6%)
Immunologic: Antibody development (DLBCL: 9%), graft versus host disease (ALL: 3%)
Nervous system: Asthenia (4% to 7%), ataxia (DLBCL: 2%), cerebral infarction (DLBCL: 1%), motor dysfunction (ALL: 1%; DLBCL: 6%), neuralgia (1% to 3%), seizure (3% to 6%), speech disturbance (including aphasia: 3% to 4%), tremor (6% to 8%)
Neuromuscular & skeletal: Myalgia (5%)
Ophthalmic: Visual impairment (3% to 6%)
Respiratory: Acute respiratory distress syndrome (ALL: 4%), flu-like symptoms (3% to 9%), oropharyngeal pain (8% to 10%), pleural effusion (5% to 10%), pulmonary infiltrates (ALL: 1%), tachypnea (3% to 10%)
Miscellaneous: Multi-organ failure (3%)
Postmarketing: Hypersensitivity: Anaphylaxis
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to tisagenlecleucel or any component of the formulation.
Concerns related to adverse effects:
• Cytokine release syndrome: Cytokine release syndrome (CRS), including fatal or life-threatening reactions, has occurred with tisagenlecleucel. Grade 3 and higher CRS reactions have occurred. The median time to onset of CRS was 3 to 4 days (range: 1 to 51 days, although onset after 10 days is rare). Half of patients with acute lymphoblastic leukemia (ALL) with CRS received tocilizumab, and some patients required addition of systemic corticosteroids. Approximately one-fifth of patients with diffuse large B-cell lymphoma (DLBCL) received tocilizumab or corticosteroids. Approximately one-fourth of the patients with follicular lymphoma (FL) received tocilizumab, with 2 patients also receiving a corticosteroid. Some patients required 2 or 3 doses of tocilizumab. One patient with DLBCL received corticosteroids without tocilizumab for CRS management; corticosteroids were used for persistent neurotoxicity following resolution of CRS (also rare). The median time to resolution of CRS was 4 to 8 days (range: 1 to 36 days). Key manifestations of CRS include fever, hypotension, hypoxia, and tachycardia, and may be associated with hepatic, renal, and cardiac dysfunction, and coagulopathy. Risk factors for severe CRS in patients with ALL are high pre-infusion tumor burden (>50% blasts in bone marrow), uncontrolled or accelerating tumor burden following lymphodepleting chemotherapy (fludarabine and cyclophosphamide), active infections, and/or inflammatory processes.
• Cytopenias: Prolonged cytopenias may occur several weeks after lymphodepleting chemotherapy and tisagenlecleucel infusion. Unresolved (by day 28 following tisagenlecleucel treatment) grade 3 or higher cytopenias included neutropenia and thrombocytopenia; some patients still experienced grade 3 or higher neutropenia or thrombocytopenia at 56 days post infusion. Prolonged neutropenia is associated with an increased risk of infection.
• Hemophagocytic lymphohistiocytosis/macrophage activation syndrome: Hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), which can be life-threatening or fatal, has occurred with tisagenlecluecel. HLH cases generally occurred during ongoing cytokine release syndrome.
• Hepatitis B virus reactivation: Hepatitis B virus (HBV) reactivation (sometimes resulting in fulminant hepatitis, hepatic failure and death) can occur in patients treated with medications directed against B cells.
• Hypersensitivity: Allergic reactions may occur with tisagenlecleucel infusion. Serious hypersensitivity reactions, including anaphylaxis, may occur due to the dimethyl sulfoxide (DMSO) or dextran 40 components in tisagenlecleucel.
• Hypogammaglobulinemia: Hypogammaglobulinemia and IgG agammaglobulinemia related to B-cell aplasia may occur in patients with a complete remission after tisagenlecleucel infusion.
• Infection: Infections (including life-threatening or fatal infections) occurred in patients after tisagenlecleucel infusion, including grades 3 and higher infections. Neutropenic fever (grade 3 or higher) has been observed after tisagenlecleucel infusion and may occur concurrently with CRS. There is no experience manufacturing tisagenlecleucel for patients with a positive HIV test or with active HBV or hepatitis C virus.
• Neurological toxicities: Neurological toxicities, which may be severe or life-threatening, can occur following treatment with tisagenlecleucel and may occur concurrently with CRS. Most neurological toxicities occurred within 8 weeks following tisagenlecleucel infusion. The median time to the first event was 5 to 8 days (range: 1 to 368 days) from infusion and the median duration was 7 days (ALL), 5 days (FL), and 17 days (DLBCL). Neurotoxicity generally resolved within 3 weeks of onset, although encephalopathy lasting up to 70 days was reported. Grade 3 and higher neurologic toxicities have been observed. The most common neurological toxicities were headache, encephalopathy, delirium, anxiety, sleep disorders, dizziness, tremor, and peripheral neuropathy; other manifestations included seizures and aphasia. The onset of neurologic toxicity may be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Due to the potential for neurologic events, including altered mental status or seizures, patients receiving tisagenlecleucel are at risk for altered or decreased consciousness or coordination in the 8 weeks following administration; during this initial period, advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery for at least 8 weeks following tisagenlecleucel infusion.
• Secondary malignancy: Patients treated with tisagenlecleucel may develop secondary malignancies or cancer recurrence. If a secondary malignancy occurs, contact the manufacturer (1-844-4KYMRIAH) to obtain patient sampling instructions for testing.
Concurrent drug therapy issues:
• Immunizations: Vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during tisagenlecleucel treatment, and until immune recovery following treatment. The safety of immunization with live vaccines during or following tisagenlecleucel treatment has not been studied.
Other warnings/precautions:
• Appropriate use: For autologous use only. Confirm availability of tisagenlecleucel prior to starting lymphodepleting regimen. Confirm patient identity and match to patient identifiers on the infusion bag(s) prior to infusion. The manufacturer recommends administering at a Risk Evaluation and Mitigation Strategy (REMS)–certified facility and with appropriate monitoring capabilities. Patients should remain within proximity of the certified facility for at least 4 weeks following infusion.
• REMS program: Tisagenlecleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYMRIAH REMS. Information is available at http://www.kymriah-rems.com or 1-844-4KYMRIAH.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the adverse/toxic effect of CAR-T Cell Immunotherapy. Specifically, the severity and duration of neurologic toxicities may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of CAR-T Cell Immunotherapy. Management: Avoid use of corticosteroids as premedication before treatment with CAR-T cell immunotherapy agents. Corticosteroids are indicated and may be required for treatment of toxicities such as cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): CAR-T Cell Immunotherapy may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary mRNA vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): CAR-T Cell Immunotherapy may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Granulocyte Colony-Stimulating Factors: May enhance the adverse/toxic effect of Tisagenlecleucel. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who could become pregnant. The duration of contraception needed following tisagenlecleucel administration is not known.
Based on the mechanism of action, if placental transfer were to occur, fetal toxicity, including B-cell lymphocytopenia, may occur. Pregnant patients who have received tisagenlecleucel may have hypogammaglobulinemia; assess immunoglobulin levels in newborns of mothers treated with tisagenlecleucel.
Data collection to monitor pregnancy and infant outcomes following exposure to tisagenlecleucel is ongoing. Pregnancies that may occur during treatment should be reported to Novartis Pharmaceuticals Corporation (888-669-6682).
Screen for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV (prior to collection of cells for manufacturing). Monitor immunoglobulin levels (after treatment). Evaluate pregnancy status (prior to therapy in sexually active patients who may become pregnant).
Monitor for signs/symptoms of cytokine release syndrome (CRS) and neurotoxicity 2 to 3 times during the first week following infusion; monitor for signs/symptoms of CRS for at least 4 weeks after treatment (evaluate immediately at the first sign of CRS); monitor for hypersensitivity reactions during infusion; monitor for signs/symptoms of infection. Monitor (life-long) for secondary malignancies.
The American Society of Clinical Oncology HBV screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy (containing human cells modified with a lentivirus) in which a patient's T cells are reprogrammed with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and normal cells. The CAR is comprised of a murine single-chain antibody fragment which recognizes CD19 and is fused to intracellular signaling domains from 4-1BB (CD137) and CD3 zeta. CD3 zeta is a critical component for initiating T-cell activation and antitumor activity, while 4-1BB enhances expansion and persistence of tisagenlecleucel. After binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the tisagenlecleucel cells. Tisagenlecleucel is prepared from the patient's peripheral blood cells obtained via leukapheresis.
Distribution: High distribution into bone marrow.
Duration: B-cell aplasia: Due to the mechanism of action, a period of B-cell aplasia is expected. In patients with B-cell acute lymphoblastic leukemia, 33% had no detectable B cells at baseline (prior to infusion); at month 24, 88% had no detectable B cell. Most patients with diffuse large B-cell lymphoma and follicular lymphoma had B-cell depletion at baseline (prior to infusion); at month 24, no patients (who had an ongoing response) had detectable B cells.
Half-life, elimination: Acute lymphoblastic leukemia (ALL): ~17 days (in responding patients); Diffuse large B-cell lymphoma (DLBCL): ~45 days (in responding patients); Follicular lymphoma: 44 days (in responding patients).
Time to peak: ~10 days (in responding patients)
Note: Tisagenlecleucel exhibits an initial rapid expansion followed by a bi-exponential decline; tisagenlecleucel is present in blood and bone marrow and is measurable beyond 2 years in patients with ALL, up to 18 months (in peripheral blood) and up to 9 months (in marrow) in patients with DLBCL, and up to 18 months (in peripheral blood) and up to 3 months (in marrow) in patients with follicular lymphoma. In patients who received tocilizumab to manage cytokine release syndrome (CRS), the tisagenlecleucel AUC and Cmax are 238% and 311% higher, respectively, in patients with DLBCL, 298% and 183% higher, respectively in patients with ALL, and 245% and 312% higher, respectively in patients with follicular lymphoma, compared with patients who did not receive tocilizumab. In patients who received corticosteroids for CRS management, the tisagenlecleucel AUC and Cmax are 104% and 179% higher, respectively, in patients with DLBCL and in patients with ALL, the AUC was 280% higher, compared with patients who did not receive corticosteroids.
Suspension (Kymriah Intravenous)
250000000CELLS (per each): $0.00
600000000CELLS (per each): $0.00
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