Safety Profile

HEPATOTOXICITY/VOD

Hepatotoxicity, including VOD, in newly diagnosed pediatric patients1
Hepatotoxicity, including life-threatening and sometimes fatal VOD, has been reported in pediatric patients with newly diagnosed AML who received MYLOTARG combination therapy
  • VOD events were reported in 25 (5%) patients in MYLOTARG plus chemotherapy arm and 25 (5%) patients in chemotherapy alone arm
  • VOD was fatal in 2 (<1%) patients in MYLOTARG plus chemotherapy arm and 7 (1%) of patients in chemotherapy alone arm
187 pediatric patients underwent HSCT in the MYLOTARG plus chemotherapy arm
  • VOD occurred within 30 days post HSCT in 20 (11%) patients
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; AML=acute myeloid leukemia; AST=aspartate aminotransferase; HSCT=hematopoietic stem cell transplantation; VOD=veno-occlusive liver disease.

SELECTED ADVERSE REACTIONS

In newly diagnosed pediatric patients with CD33-positive AML, MYLOTARG demonstrated a favorable risk-benefit profile1
Fatal events
  • In the MYLOTARG plus chemotherapy arm, fatal adverse reactions were infection (14 [3%]), multi-organ failure (5 [1%]), anemia (1 [<1%]), and hemorrhage (3 [<1%])
  • In the chemotherapy alone arm, fatal adverse reactions included infection (7 [1%]), multi-organ failure (6 [1%]), hepatic failure (1 [<1%]), hypotension (3 [<1%]), and hemorrhage (3 [<1%])
Prolonged cytopenias during Intensification 2
  • The addition of MYLOTARG to chemotherapy was associated with a higher incidence of prolonged thrombocytopenia and neutropenia, particularly when used in Intensification 2
  • Prolonged thrombocytopenia* was reported in 190/297 (64%) patients in MYLOTARG plus chemotherapy arm vs 146/264 (55%) in chemotherapy alone arm
  • Prolonged neutropenia occurred in 142/300 (47%) patients in MYLOTARG plus chemotherapy arm vs 118/275 (43%) in chemotherapy alone arm
  • Prolonged cytopenias were associated with more deaths in remission in the MYLOTARG plus chemotherapy arm (29 [5%]) vs chemotherapy alone arm (15 [3%])
Additional safety considerations
  • The safety and effectiveness of single-agent MYLOTARG in pediatric patients with newly diagnosed AML has not been established
  • The safety and effectiveness of MYLOTARG plus chemotherapy in pediatric patients less than 1 month of age with newly diagnosed AML has not been established
*Prolonged thrombocytopenia was defined as platelets less than 50 Gi/L lasting past cycle Day 42 in the absence of active leukemia.
Prolonged neutropenia was defined as neutrophils less than 0.5 Gi/L lasting past cycle Day 42 in the absence of active leukemia.
AML=acute myeloid leukemia.

HEMORRHAGE

Hemorrhage in newly diagnosed pediatric patients in the MYLOTARG plus chemotherapy arm1
  • MYLOTARG is myelosuppressive and can cause fatal or life-threatening hemorrhage due to prolonged thrombocytopenia
  • Fatal bleeding occurred in 3/520 (<1%) patients in the MYLOTARG plus chemotherapy arm
  • Grade 3 or 4 bleeding was reported in 66/520 (13%) patients in the MYLOTARG plus chemotherapy arm
  • 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
REFERENCE
1. MYLOTARG Prescribing Information. New York, NY: Pfizer Inc.