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

Overview

This single-arm interventional study evaluated the short-term outcome of one 28-day cycle of venetoclax combined with a hypomethylating agent (azacitidine or decitabine) in adults with newly diagnosed acute myeloid leukemia who could not receive intensive induction chemotherapy. Twenty-four patients were enrolled at the Department of Haematology, Dhaka Medical College Hospital, Dhaka, Bangladesh. In addition to older and comorbid patients, the cohort included younger patients for whom intensive chemotherapy was financially inaccessible - a population under-represented in existing trial and registry data. The primary endpoint was the composite remission rate (complete remission plus complete remission with incomplete haematologic recovery) assessed by bone marrow examination on Day 28. Secondary endpoints included change in complete blood count parameters, treatment-emergent adverse events, and 28-day mortality.

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.