Safety Profile

HEPATOTOXICITY/VOD

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.

ADVERSE EVENTS

MYLOTARG demonstrated a favorable safety profile in the relapsed setting, with no reported Grade 4 toxicity1
  • All 57 patients in the study were able to receive the 3 planned doses of MYLOTARG
  • No Grade 4 toxicity was reported
  • No deaths occurred from infections
ALT=alanine aminotransferase; AST=aspartate aminotransferase; TEAE=treatment-emergent adverse event.
REFERENCE
1. MYLOTARG Prescribing Information. New York, NY: Pfizer Inc.