What is the initial treatment for acute myeloid leukemia (AML)?

Initial Treatment for Acute Myeloid Leukemia (AML)

The initial treatment for acute myeloid leukemia consists of induction chemotherapy with a standard "7+3" regimen of cytarabine for 7 days plus an anthracycline (typically daunorubicin) for 3 days, with treatment modifications based on patient-specific factors including age, cytogenetics, and molecular markers. 1

Patient Stratification for Initial Treatment

Treatment approach should be determined based on:

1. Patient Factors

• Age: ≥60 years vs <60 years
• Performance status and comorbidities: Determines eligibility for intensive chemotherapy
• Cardiac function: Echocardiography recommended before anthracycline therapy 1

2. Disease Characteristics

• Cytogenetics: Favorable, intermediate, or adverse risk
• Molecular markers: FLT3, NPM1, IDH1/2, etc.
• AML subtype: De novo, therapy-related (t-AML), or AML with myelodysplasia-related changes (AML-MRC)

Treatment Algorithm

For Patients Eligible for Intensive Chemotherapy:

Core Binding Factor (CBF) AML (favorable risk):

• 7+3+GO: 7 days cytarabine + 3 days daunorubicin + gemtuzumab ozogamicin (for CD33+ AML) 1

FLT3-mutated AML:

• 7+3+midostaurin: Standard induction plus midostaurin 1

Therapy-related AML or AML-MRC:

• CPX-351: Liposomal formulation of daunorubicin and cytarabine (especially for patients ≥60 years) 1

Standard risk AML without specific mutations:

• 7+3 regimen: Cytarabine (100-200 mg/m²) continuous infusion for 7 days + anthracycline (daunorubicin 60-90 mg/m² or idarubicin 12 mg/m²) for 3 days 1, 2

For Patients Not Eligible for Intensive Chemotherapy:

• Venetoclax + hypomethylating agent: Azacitidine or decitabine 1
• Venetoclax + low-dose cytarabine (LDAC) 1
• Glasdegib + LDAC 1
• Hypomethylating agents alone: Azacitidine or decitabine 1, 3
• IDH1/2 inhibitors: Ivosidenib (IDH1) or enasidenib (IDH2) for patients with respective mutations 1

Response Assessment

• Bone marrow evaluation should be performed 14-21 days after start of induction therapy 1
• For patients receiving intensive therapy, marrow evaluation should be performed after 4-6 weeks to document remission status 1
• For patients receiving lower-intensity therapy, marrow evaluation should be performed after 8-12 weeks 1

Important Considerations

• Clinical trials should always be considered and are strongly encouraged 1
• Supportive care is essential, including prophylaxis for tumor lysis syndrome and management of infections
• Allogeneic stem cell transplantation should be considered early in treatment planning for eligible intermediate and high-risk patients 1
• Central venous access is necessary for patients receiving intensive chemotherapy 1

Pitfalls to Avoid

• Delaying treatment unnecessarily: While diagnostic workup is important, excessive delays should be avoided, particularly in patients with hyperleukocytosis or symptoms of leukostasis
• Undertreatment of fit elderly patients: Age alone should not exclude patients from intensive therapy; functional status and comorbidities are more important determinants 1, 4
• Overtreatment of unfit patients: Intensive chemotherapy in patients with poor performance status can lead to treatment-related mortality without improving outcomes
• Neglecting molecular testing: Treatment decisions increasingly depend on specific genetic markers that guide targeted therapies 1

The landscape of AML treatment is rapidly evolving with new targeted agents showing improved outcomes compared to standard 7+3 chemotherapy alone 5. However, intensive induction chemotherapy remains the backbone of treatment for fit patients with AML, offering the best chance for long-term remission, especially when followed by appropriate consolidation therapy 4.