What is the initial treatment for Acute Myeloid Leukemia (AML)?

Initial Treatment for Acute Myeloid Leukemia (AML)

The standard initial treatment for newly diagnosed AML is the "7+3" regimen consisting of 7 days of cytarabine and 3 days of daunorubicin, with the addition of gemtuzumab ozogamicin (GO) for CD33-positive disease. 1

Treatment Algorithm Based on Patient Characteristics

For Patients Eligible for Standard Induction Therapy

1. Core Binding Factor (CBF) AML:

   • 7+3 regimen: 7 days of standard-dose cytarabine + 3 days of daunorubicin
   • Add gemtuzumab ozogamicin (GO) if CD33-positive (in induction cycle 1) 1
   • GO dosing: Either 3 mg/m² on days 1,4, and 7 or a single dose of 3 mg/m² during induction cycle 1

2. Therapy-related AML (tAML) or AML with myelodysplasia-related changes (MRC-AML) in patients ≥60 years:

   • CPX-351 (liposomal daunorubicin and cytarabine) 1

3. Standard-risk AML without specific genetic markers:

   • 7+3 regimen: 7 days of standard-dose cytarabine + 3 days of daunorubicin 1
   • Consider higher dose daunorubicin (90 mg/m²) for patients <60 years 1, 2

For Patients Not Eligible for Standard Induction Therapy

1. Older/frail patients:
   • Hypomethylating agents (HMA) with or without venetoclax 1, 3
   • Low-dose cytarabine with or without venetoclax 1

Premedication and Supportive Care

Before starting induction therapy:

• Assess for active infection and treat if present 1
• Obtain cardiac evaluation including echocardiography 1
• Insert central venous catheter (under platelet transfusion if needed) 1
• For patients with hyperleukocytosis (WBC >100×10⁹/L):
  • Administer hydroxycarbamide (50-60 mg/kg/day) or cytarabine 1
  • Leukapheresis is not generally recommended 1
• For suspected APL: Start ATRA immediately pending confirmation 1

Response Assessment

• Bone marrow evaluation 14-21 days after start of induction 1, 4
• Response categories:
  • Complete remission (CR)
  • Residual disease with hypoplasia
  • Residual disease without hypoplasia (induction failure)

Consolidation Therapy

For patients achieving CR:

• CBF-AML: Multiple cycles of intermediate-dose cytarabine (IDAC) with GO added to consolidation cycles 1 and 2 for CD33+ disease 1, 4
• Consider autologous stem cell transplantation as an alternative to multiple IDAC cycles 1

Important Considerations and Caveats

• CD33 expression: Verify CD33 expression in ≥30% of blasts before administering GO 4, 5
• GO toxicity: Monitor for hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) 5
• Transplant timing: Wait at least 2 months between the last GO dose and hematopoietic stem cell transplantation conditioning 1, 4
• Daunorubicin dosing: Higher dose daunorubicin (90 mg/m²) has shown improved complete remission rates and overall survival in patients <60 years compared to standard dose (45 mg/m²) 2
• Treatment failure: For patients with residual disease after induction, additional standard-dose cytarabine with anthracycline or escalation to high-dose cytarabine should be considered 1

Emerging Therapies

Recent advances have expanded treatment options beyond the traditional 7+3 regimen:

• Molecularly targeted therapies for specific mutations (FLT3, IDH1, IDH2) 3
• Hypomethylating agents combined with venetoclax for older adults 3

The selection of initial therapy should be guided by patient age, performance status, cytogenetic and molecular profile, and comorbidities to maximize survival outcomes while minimizing treatment-related toxicity.