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  • Newly Diagnosed Adult AML (Combination Regimen)
    Newly Diagnosed Pediatric AML (Combination Regimen)
    Newly Diagnosed Adult AML (Single-Agent-Regimen)
    Relapsed or Refractory AML (Single-Agent-Regimen)
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    Newly Diagnosed Adult AML (Combination Regimen)
    Newly Diagnosed Pediatric AML (Combination Regimen)
    Newly Diagnosed Adult AML (Single-Agent-Regimen)
    Relapsed or Refractory AML (Single-Agent-Regimen)

    Safety Profile

    ​​​​​​​Relapsed or Refractory AML (Single-Agent Regimen)
    HEPATOTOXICITY/VOD ADVERSE EVENTS

    Hepatotoxicity, including VOD1

    • Hepatotoxicity, including life-threatening and sometimes fatal VOD events, has been reported in patients receiving MYLOTARG as a single agent or as part of a combination chemotherapy regimen
    • In this Phase 2 single-arm study in the relapse setting, VOD events were reported in none of the 57 patients during or following treatment, or following HSCT after completion of MYLOTARG treatment
    • In this study, HSCT was allowed after treatment with MYLOTARG, but an interval of at least 90 days between the last dose of MYLOTARG and HSCT was recommended

    Factors associated with increased risk of VOD1,2

    Based on an analysis across trials using MYLOTARG as a single agent, primarily at a 9 mg/m2 dose, the following factors were associated with an increased risk of VOD:
    ​​​​​​​
    • Higher doses of MYLOTARG as monotherapy in adult patients
    • HSCT before or following treatment with MYLOTARG
    • Moderate/severe hepatic impairment prior to treatment​​​​​​​

    Strategies to manage hepatotoxicity, including VOD1

    Prior to each dose of MYLOTARG

    • Assess ALT, AST, total bilirubin, and alkaline phosphatase
    After treatment with MYLOTARG

    • Monitor frequently for signs and symptoms of VOD, such as:
      • Elevations in ALT or AST
      • Elevations in total bilirubin
      • Rapid weight gain
      • Ascites
      • Hepatomegaly (which may be painful)
    • Monitoring only total bilirubin may not identify all patients at risk of VOD
    • For patients who develop abnormal liver tests, more frequent monitoring of liver tests and clinical signs and symptoms of hepatotoxicity is recommended
    • Manage signs or symptoms of hepatic toxicity by dose interruption or discontinuation of MYLOTARG. In patients who experience VOD, discontinue MYLOTARG and treat according to standard medical practice
    Patients proceeding to HSCT

    • Although no relationship was found between VOD and time of HSCT relative to higher MYLOTARG monotherapy doses, in MyloFrance-1, no patients underwent HSCT within 3.5 months of MYLOTARG therapy
    • Monitor liver tests frequently during the post-HSCT period, as appropriate

    ALT=alanine aminotransferase; AST=aspartate aminotransferase; HSCT=hematopoietic stem cell transplant; VOD=veno-occlusive liver disease.


    References:
    1. MYLOTARG Prescribing Information. New York, NY: Pfizer Inc.
    2. Data on file. Pfizer Inc., New York, NY.

    Relapsed or Refractory AML (Single-Agent Regimen)

    • Efficacy
    • Study Design
    • Safety Profile
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    Indications

    MYLOTARG™ (gemtuzumab ozogamicin) is indicated for the treatment of:

    • Newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients 1 month and older
    • Relapsed or refractory CD33-positive AML in adults and pediatric patients 2 years and older

    WARNING: Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of MYLOTARG as a single agent, and as part of a combination chemotherapy regimen. Monitor frequently for signs and symptoms of VOD after treatment with MYLOTARG.

    Contraindications: Hypersensitivity to MYLOTARG or any of its components. Reactions have included anaphylaxis.

    Hepatotoxicity, Including Veno-occlusive Liver Disease (VOD): Hepatotoxicity, including life-threatening and sometimes fatal hepatic VOD events, have been reported in patients receiving MYLOTARG as a single agent or as part of a combination chemotherapy regimen. Based on an analysis across trials, the risk of VOD was higher in adult patients who received higher doses of MYLOTARG as monotherapy, in patients with moderate or severe hepatic impairment prior to receiving MYLOTARG, in patients treated with MYLOTARG after HSCT, and in patients who underwent HSCT after treatment with MYLOTARG. Although no relationship was found between VOD and time of HSCT relative to higher MYLOTARG monotherapy doses, the ALFA-0701 study recommended an interval of 2 months between the last dose of MYLOTARG and HSCT. Assess ALT, AST, total bilirubin, and alkaline phosphatase prior to each dose of MYLOTARG. After treatment with MYLOTARG, monitor frequently for signs and symptoms of VOD; these may include elevations in ALT, AST, and total bilirubin, hepatomegaly, rapid weight gain, and ascites. Monitoring only total bilirubin may not identify all patients at risk of VOD. For patients who develop abnormal liver tests, more frequent monitoring of liver tests and clinical signs and symptoms of hepatotoxicity is recommended. For patients who proceed to HSCT, monitor liver tests frequently during the post-HSCT period, as appropriate. Manage signs or symptoms of hepatic toxicity by dose interruption or discontinuation of MYLOTARG. In patients who experience VOD, discontinue MYLOTARG and treat according to standard medical practice.

    Infusion-Related Reactions (Including Anaphylaxis): Life-threatening or fatal infusion-related reactions can occur during or within 24 hours following infusion of MYLOTARG. Signs and symptoms of infusion-related reactions may include fever, chills, hypotension, tachycardia, hypoxia, and respiratory failure. Premedicate prior to MYLOTARG infusion. Monitor vital signs frequently during infusion. Interrupt infusion immediately for patients who develop evidence of infusion reaction, especially dyspnea, bronchospasm, or hypotension. Monitor patients during and for at least 1 hour after the end of the infusion or until signs and symptoms completely resolve. Discontinue use of MYLOTARG in patients who develop signs or symptoms of anaphylaxis, including severe respiratory symptoms or clinically significant hypotension.

    Hemorrhage: MYLOTARG is myelosuppressive and can cause fatal or life-threatening hemorrhage due to prolonged thrombocytopenia. In ALFA-0701, (MYLOTARG in combination with chemotherapy), all grades and Grade 3-4 bleeding events were reported in 118/131 (90%) and 27/131 (21%) patients, respectively. Fatal bleeding events (including cerebral hematoma, intracranial hematoma, and subdural hematoma) occurred in 4/131 (3%) patients. The proportion of patients with persistent thrombocytopenia increased with progressive treatment phases and was higher in patients treated with MYLOTARG plus chemotherapy than with chemotherapy alone. In AAML0531, the addition of MYLOTARG to chemotherapy in pediatric patients was associated with a higher incidence of prolonged thrombocytopenia and neutropenia particularly when used in Intensification 2. Assess blood counts prior to each dose of MYLOTARG and monitor blood counts frequently after treatment with MYLOTARG until resolution of cytopenias. Monitor patients for signs and symptoms of bleeding during treatment with MYLOTARG. Manage severe bleeding, hemorrhage, or persistent thrombocytopenia using dose delay or permanent discontinuation of MYLOTARG, and provide supportive care per standard practice.

    QT Interval Prolongation: QT interval prolongation has been observed in patients treated with other drugs containing calicheamicin. When administering MYLOTARG to patients who have a history of or predisposition for QTc prolongation, who are taking medicinal products that are known to prolong QT interval, and in patients with electrolyte disturbances, obtain electrocardiograms and electrolytes prior to the start of treatment and as needed during administration.

    Adverse Cytogenetics: In a subgroup analysis in ALFA-0701, the addition of MYLOTARG to standard combination chemotherapy did not improve event-free survival in the subgroup of patients having adverse-risk cytogenetics. For patients being treated with MYLOTARG in combination with daunorubicin and cytarabine for newly diagnosed de novo AML, when cytogenetics testing results become available consider whether the potential benefit of continuing treatment with MYLOTARG outweighs the risks for the individual patient.

    Embryo-Fetal Toxicity: MYLOTARG can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with MYLOTARG and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with MYLOTARG and for at least 3 months after the last dose.

    Adverse Reactions: All grade treatment-emergent adverse events (>15%) in adult patients exposed to MYLOTARG 3 mg/m2 on Days 1, 4, and 7 as monotherapy included fever (79%), infection (42%), increased AST (40%), bleeding (23%), nausea and vomiting (21%), constipation (21%), mucositis (21%), headache (19%), increased ALT (16%), and rash (16%). In a study of newly diagnosed pediatric patients 1 month and older (AAML0531), in the MYLOTARG + chemotherapy arm, grade 3 or 4 adverse reactions (≥15%) during induction 1 included infection (36%), febrile neutropenia (32%), and decreased appetite (15%); grade 3 or 4 adverse reactions (≥15%) during intensification 2 included infection (67%), febrile neutropenia (24%), and decreased appetite (19%).

    MYLOTARG is indicated for the treatment of​​​​​​​

    • Newly diagnosed CD33-positive acute myeloid leukemia (AML) in adults and pediatric patients 1 month and older
    • Relapsed or refractory CD33-positive AML in adults and pediatric patients 2 years and older

    Please see full Prescribing Information, including BOXED WARNING.