Venetoclax With Hypomethylating Agents in Newly Diagnosed AML Unfit for Intensive Chemotherapy

Background and Rationale

Acute myeloid leukemia (AML) predominantly affects older adults, who often cannot tolerate intensive induction chemotherapy due to comorbidity or poor performance status. In low- and middle-income countries like Bangladesh, a secondary population-younger, medically fit patients-is also unable to receive intensive therapy due to prohibitive costs. While hypomethylating agents (HMAs) combined with venetoclax represent a standard lower-intensity approach, real-world data on this regimen are lacking in Bangladesh and sparse for financially constrained younger cohorts. This study evaluates the short-term outcomes of a single cycle of venetoclax plus an HMA in both groups at a public tertiary care hospital.

Intervention Details & Dosing Nuances

Participants receive one 28-day cycle consisting of either IV azacitidine (75 mg/m² daily on Days 1-7) or IV decitabine (20 mg/m² daily on Days 1-5), based on physician discretion. Oral venetoclax is administered at 100 mg on Day 1, 200 mg on Day 2, and maintained at 100 mg daily from Day 3 to Day 28. The venetoclax dose is intentionally capped at 100 mg daily (instead of standard higher dosing) because all participants receive concomitant oral voriconazole (200 mg twice daily, Days 3-28) for antifungal prophylaxis, a strong CYP3A4 inhibitor requiring mandatory venetoclax dose reduction. Tumour lysis syndrome prophylaxis and standard supportive care (transfusions, antimicrobials) are provided per institutional protocols.

Inclusion criteria

• Newly diagnosed acute myeloid leukemia
• Age 18 years or older
• Deemed ineligible for intensive chemotherapy by the treating physician based on age (≥60 years), performance status or comorbidity, financial constraints, or patient unwillingness to receive intensive chemotherapy
• Written informed consent

Exclusion criteria

• Acute promyelocytic leukemia
• Previous treatment with a hypomethylating agent