Tisagenlecleucel

Dosage Forms

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]

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

High distribution into bone marrow.

Time to Peak

~10 days (in responding patients)

Half-Life Elimination

ALL: ~17 days (in responding patients); DLBCL: ~45 days (in responding patients)

Use: Labeled Indications

Acute lymphoblastic leukemia (relapsed or refractory): Treatment of B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse in patients up to 25 years of age.

Diffuse large B-cell lymphoma (relapsed or refractory): Treatment of relapsed or refractory large B-cell lymphoma in adults (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.

Limitation of use: Not indicated for treatment of primary CNS lymphoma.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosage and Administration

Dosing: Adult

Note: For autologous use only; confirm patient identity on each bag prior to infusion. A single dose may be contained in up to 3 patient-specific infusion bags (acute lymphoblastic leukemia [ALL] doses are contained in a single infusion bag); 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. 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.

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 x 10⁶ CAR-positive viable T cells per kg body weight

<25 years and >50 kg: IV: 0.1 to 2.5 x 10⁸ CAR-positive viable T cells

Diffuse large B-cell lymphoma (relapsed or refractory): IV: 0.6 to 6 x 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 WBC ≤1,000/mm³ within 1 week prior to tisagenlecleucel infusion.

Dosing: Pediatric

For autologous use only; confirm patient identity prior to prescribing.

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 graft versus host disease (GVHD), or increasing leukemia burden following lymphodepleting chemotherapy.

Premedicate with acetaminophen and diphenhydramine (or another H₁-antihistamine) ~30 to 60 minutes prior to tisagenlecleucel infusion. Do not use corticosteroids at any time (except for life-threatening situations). Refer to the certificate of analysis for the actual number of CAR-positive T cells in tisagenlecleucel provided in patient-specific product.

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.

Dosing adjustment for toxicity: 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.

Dosing: Adjustment for Toxicity

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, 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 (patients ≥30 kg: tocilizumab 8 mg/kg; maximum tocilizumab dose: 800 mg; 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.

Reconstitution

Inspect patient specific infusion bag(s) for breaks or cracks prior to thawing (if bag is compromised, contact manufacturer). Place infusion bag inside a second sterile bag in case of leaks and to protect ports from contamination. If more than 1 bag has been received for the treatment dose, thaw 1 bag at a time. Wait to thaw/infuse the next bag until it is determined that the previous bag is safely administered. Thaw at 37°C using a water bath or dry thaw method until there is no visible ice in the infusion bag, remove bag from thawing device immediately (once thawed and at room temperature, infuse within 30 minutes). Do not wash, spin down, and/or resuspend tisagenlecleucel in new media prior to infusion. 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, if the infusion bag is damaged or leaking, or if it otherwise appears to be compromised (contact manufacturer).

Administration

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 (doses for ALL will be contained in a single infusion bag).

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.

Storage

Store infusion bag(s) (frozen suspension) in the vapor phase of liquid nitrogen (≤-120°C), in a temperature-monitored system. After thawing, may only be stored for up to 30 minutes at room temperature of 20°C to 25°C.

Drug Interactions

Corticosteroids (Systemic): May diminish the therapeutic effect of Tisagenlecleucel. Management: Avoid use of corticosteroids as premedication or at any time during treatment with tisagenlecleucel, except in the case of life-threatening emergency (such as resistant cytokine release syndrome). Consider therapy modification

Granulocyte Colony-Stimulating Factors: May enhance the adverse/toxic effect of Tisagenlecleucel. Avoid combination

Vaccines (Live): Tisagenlecleucel may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Tisagenlecleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for two weeks prior to initiation of lymphodepleting therapy, during tisagenlecleucel infusion, and after treatment until full immune recovery is achieved. Consider therapy modification

Test Interactions

May result in false positive results with some commercial HIV nucleic acid tests.

Adverse Reactions

>10%:

Cardiovascular: Hypotension (26% to 31%), tachycardia (children, adolescents, and adults: 26%; adults: 13%), edema (21% to 23%), hypertension (children, adolescents, and adults: 19%; adults: 2%)

Central nervous system: Headache (children, adolescents, and adults: 37%; adults: 21%), encephalopathy (children, adolescents, and adults: 34%; adults: 16%), fatigue (25% to 26%), delirium (children, adolescents, and adults: 21%; adults: 6%), pain (15% to 18%), chills (10% to 13%), anxiety (9% to 13%), dizziness (6% to 11%)

Dermatologic: Skin rash (8% to 16%)

Endocrine & metabolic: Hypokalemia (children, adolescents, and adults; grades 3/4: 27%; adults, grades 3/4: 12%), hypophosphatemia (grades 3/4: 19% to 24%), hyponatremia (adults, grades 3/4: 11%), weight loss (adults: 11%)

Gastrointestinal: Decreased appetite (children, adolescents, and adults: 37%; adults: 12%), vomiting (children, adolescents, and adults: 26%; adults: 9%), diarrhea (26% to 31%), nausea (26% to 27), constipation (16% to 18%), abdominal pain (9% to 16%)

Hematologic & oncologic: Anemia (children, adolescents, and adults: 100%; adults, grades 3/4: 58%), neutropenia (children, adolescents, and adults: 100%; grades 3/4: 17% to 40%; adults, grades 3/4: 81%), thrombocytopenia (children, adolescents, and adults: 100%; grades 3/4: 12% to 27%; adults, grades 3/4: 54%), lymphocytopenia (adults, grades 3/4: 94%), leukopenia (adults, grades 3/4: 77%), hypogammaglobulinemia (children, adolescents, and adults: 43%; adults: 14%; grades ≥3: 4% to 7%), febrile neutropenia (children, adolescents, and adults: 37%; grades ≥3: 37%; adults: 17%; grades ≥3: 17%), hypofibrinogenemia (children, adolescents, and adults; grades 3/4: 16%; with cytokine release syndrome), increased INR (children, adolescents, and adults: 13%)

Hepatic: Increased serum aspartate aminotransferase (children, adolescents, and adults; grades 3/4: 28%), increased serum alanine aminotransferase (children, adolescents, and adults; grades 3/4: 21%), increased serum bilirubin (children, adolescents, and adults; grades 3/4: 21%)

Hypersensitivity: Cytokine release syndrome (74% to 79%)

Infection: Infection (41% to 55%; unknown pathogen), viral infection (children, adolescents, and adults: 26%; adults: 9%), bacterial infection (children, adolescents, and adults: 19%; adults: 9%), fungal infection (9% to 13%)

Neuromuscular & skeletal: Myalgia (7% to 15%), arthralgia (10% to 12%)

Renal: Acute renal failure (17% to 24%)

Respiratory: Hypoxia (children, adolescents, and adults: 24%; adults: 8%), cough (19% to 21%), dyspnea (16% to 18%), pulmonary edema (children, adolescents, and adults: 16%; adults: 3%), tachypnea (children, adolescents, and adults: 12%)

Miscellaneous: Fever (34% to 40%)

1% to 10%:

Cardiovascular: Cardiac failure (children, adolescents, and adults: 7%), thrombosis (3% to 7%), cardiac arrhythmia (adults: 6%), capillary leak syndrome (1% to 3%), cerebral infarction (adults: 1%)

Central nervous system: Sleep disorder (9% to 10%), peripheral neuropathy (4% to 8%), motor dysfunction (adults: 6%; children, adolescents, and adults: 1%), seizure (3%), speech disturbance (3%), ataxia (adults: 2%)

Dermatologic: Dermatitis (adults: 4%)

Endocrine & metabolic: Fluid retention (children, adolescents, and adults: 10%; adults: 3%)

Gastrointestinal: Abdominal distress (abdominal compartment syndrome; children, adolescents, and adults: 1%), fecal incontinence (adults: 1%)

Hematologic & oncologic: Disseminated intravascular coagulation (children, adolescents, and adults: 9%; adults: 3%), lymphocytosis (histiocytosis lymphoticytic hemophagocytosis; children, adolescents, and adults: 7%; adults: 1%), disorder of hemostatic components of blood (children, adolescents, and adults: 6%), prolonged partial thromboplastin time (children, adolescents, and adults: 6%), tumor lysis syndrome (children, adolescents, and adults: 6%; adults: 1%), pancytopenia (adults: 2%),

Immunologic: Antibody development (adults: 5%), graft versus host disease (children, adolescents, and adults: 1%)

Neuromuscular & skeletal: Back pain (6% to 10%), tremor (7% to 9%), asthenia (adults: 7%)

Ophthalmic: Visual impairment (3% to 7%)

Respiratory: Nasal congestion (children, adolescents, and adults: 10%), pleural effusion (5% to 10%), oropharyngeal pain (6% to 8%), respiratory distress (children, adolescents, and adults: 6%), respiratory failure (children, adolescents, and adults: 6%), acute respiratory distress (children, adolescents, and adults: 4%)

Miscellaneous: Multi-organ failure (3%)

Frequency not defined: Central nervous system: Aphasia, mutism

Warnings/Precautions

Concerns related to adverse effects:

• Cytokine release syndrome: [US Boxed Warning]: 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 with tocilizumab and corticosteroids. Grade 3 and higher CRS reactions have occurred. The median time to onset of CRS was 3 days (range: 1 to 51 days, although onset after 10 days is rare). Half of ALL patients with CRS received tocilizumab and some patients required addition of corticosteroids (methylprednisolone). Approximately one-fifth of patients with DLBCL received tocilizumab or corticosteroids. Some patients required 2 or 3 doses of tocilizumab. In rare instances, patients 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 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; risk factors for developing severe CRS in DLBCL are not known. Delay tisagenlecleucel infusion after lymphodepleting chemotherapy for 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 leukemia burden. Ensure that tocilizumab is available (a minimum of 2 doses) on site prior to tisagenlecleucel infusion. Monitor for signs or symptoms of CRS for at least 4 weeks after treatment (monitor 2 to 3 times during the first week after infusion). Patients should seek immediate medical attention if signs or symptoms of CRS occur at any time. Evaluate patients immediately at the first sign of CRS; hospitalize and begin supportive care, tocilizumab and/or corticosteroids as indicated.
• 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. Myeloid growth factors, particularly GM-CSF (sargramostim), are not recommended during the first 3 weeks after tisagenlecleucel infusion or until CRS has resolved.
• 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. Screen for HBV, HCV, and HIV in accordance with clinical guidelines prior to collection of cells for manufacturing.
• 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 (CR) after tisagenlecleucel infusion. Monitor immunoglobulin levels after tisagenlecleucel treatment. Manage hypogammaglobulinemia with infection precautions, antibiotic prophylaxis and immunoglobulin treatment (per standard replacement guidelines). Pregnant women who have received tisagenlecleucel may have hypogammaglobulinemia; assess immunoglobulin levels in newborns of mothers treated with tisagenlecleucel.
• Infection: Infections (including life-threatening or fatal infections) occurred in patients after tisagenlecleucel infusion, including grades 3 and higher infections. Begin prophylaxis according to local guidelines prior to tisagenlecleucel infusion. Delay tisagenlecleucel infusion for active uncontrolled infection until after resolution. Monitor for signs and symptoms of infection following treatment and manage appropriately. Neutropenic fever (grade 3 or higher) has been observed after tisagenlecleucel infusion and may occur concurrently with CRS. If neutropenic fever occurs, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as clinically indicated.
• Neurological toxicities: [US Boxed Warning]: Neurological toxicities, which may be severe or life-threatening, can occur following treatment with tisagenlecleucel, and may occur concurrently with CRS. Monitor for neurological events after treatment and provide supportive care as needed; if neurologic symptoms occur, exclude other causes. Monitor for neurotoxicity 2 to 3 times during the first week following infusion. Most neurological toxicities occurred within 8 weeks following tisagenlecleucel infusion. The median time to the first event was 6 days (range: 1 to 359 days) from infusion and the median duration was 6 days (ALL) and 14 days (DLBCL). Neurotoxicity generally resolved within 21 days of onset, although encephalopathy lasting up to 50 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, mutism, 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.
• Secondary malignancy: Patients treated with tisagenlecleucel may develop secondary malignancies or cancer recurrence. Monitor (life-long) for secondary malignancies. If a secondary malignancy occurs, contact the manufacturer (1-844-4KYMRIAH) to obtain patient sampling instructions for testing.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Immunizations: Vaccination with live virus 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 viral 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 certified facility and monitoring 2 to 3 times during the first week following infusion for signs/symptoms of CRS and neurotoxicity. Patients should remain within proximity of the certified facility for at least 4 weeks following infusion.
• REMS program: [US Boxed Warning]: 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.

Monitoring Parameters

Screen for HBV, HCV, and HIV (prior to collection of cells for manufacturing). Monitor immunoglobulin levels (after treatment). Pregnancy testing (prior to therapy in sexually active females of reproductive potential).

Monitor for signs/symptoms of 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, neurologic toxicity, signs/symptoms of infection. Monitor (life-long) for secondary malignancies.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted. If placental transfer were to occur, fetal toxicity, including B-cell lymphocytopenia may occur. Pregnant women who have received tisagenlecleucel may have hypogammaglobulinemia; assess immunoglobulin levels in newborns of mothers treated with tisagenlecleucel.

The duration of contraception needed following tisagenlecleucel administration is not known.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience lack of appetite, nausea, vomiting, diarrhea, constipation, abdominal pain, painful extremities, muscle pain, joint pain, back pain, weight loss, or stuffy nose. Have patient report immediately to prescriber signs of cytokine release syndrome (chills, dizziness, loss of strength and energy, fever, headache, passing out, rash, swelling in your throat, difficulty breathing, nausea, vomiting, or wheezing), signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), anxiety, confusion, nervousness, agitation, restlessness, vision changes, dizziness, passing out, sensing things that seem real but are not, headache, seizures, tremors, difficulty speaking, behavioral changes, mood changes, shortness of breath, excessive weight gain, swelling of arms or legs, fast breathing, severe loss of strength and energy, or fast heartbeat (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.