Outpatient Low-Dose Venetoclax-Azacitidine vs. Intensive Therapy in Newly Diagnosed AML in Resource-Limited Settings Open Access

1. Outpatient low-dose VenAza plus itraconazole reduced early mortality and hospitalizations while maintaining treatment efficacy.

2. VenAza offers a safer, cost-effective alternative to intensive chemotherapy in newly diagnosed AML.

Acute myeloid leukemia (AML) treatment in fit adults traditionally relies on intensive chemotherapy, but access to supportive care and inpatient capacity limits its feasibility in low-resource settings. Venetoclax, a BCL-2 inhibitor, has shown promise in unfit AML patients, but its role in induction-eligible adults remains unclear. We retrospectively compared an outpatient regimen combining low-dose venetoclax, itraconazole, and azacitidine (VenAza) versus intensive chemotherapy in 100 adults with newly diagnosed AML. Forty-four received low-dose VenAza and 56 intensive therapy. The VenAza group had significantly fewer complications (54.5% vs. 98.1%, p=.0001), due to lower febrile neutropenia rates (50% vs. 90.6%, p=.0001). Half of the VenAza group remained ambulatory during induction (50% vs. 1.8%, p=.0001), had shorter hospital stays (median 14 vs. 28 days, p=.0001) and reduced 60-day mortality (4.5% vs. 26.8%, p=.003). Response rates were comparable (59.5% vs. 76.9%, p=.10), and relapse-free survival was significantly longer with VenAza (not reached vs. 6.2 months, p=.017). The incidence of relapse was also lower (p=.002). VenAza showed similar overall survival (10.1 vs. 9.0 months; p = .097). Landmark and Cox analyses confirmed these findings, with VenAza independently associated with improved OS (HR 1.82, p = .039) and RFS (HR 3.23, p = .043), and a trend for EFS (HR 1.72, p = .061). Outpatient VenAza reduced hospitalizations, early deaths, and complications, while maintaining efficacy. This strategy may represent a safer, cost-effective alternative to intensive chemotherapy for induction-eligible AML patients in low-resource settings, potentially informing global practice where supportive care is limited.