Venetoclax for unfit AML: real-world outcomes of standard and azole-adjusted dosing in Brazilian public and private care

Intensive induction therapy is often not feasible in unfit adults with acute myeloid leukemia (AML), and venetoclax-based regimens have become the standard of care for this population, although access to these drugs remains limited in many low- and middle-income countries (LMICs), where azole-adjusted dosing has emerged as a strategy to enable venetoclax use. We conducted a retrospective study of 160 unfit AML patients treated at Brazilian public and private centers to compare outcomes with azole-adjusted versus full-dose venetoclax-based regimens. In the public center, 54 patients received continuously azole-adjusted venetoclax combinations, whereas in the private center, 41 patients received venetoclax at the full target dose (400 mg daily), with temporary dose reduction only during intermittent azole prophylaxis. Composite complete remission rates were 54% in the public azole-adjusted cohort and 68.3% in the private cohort, with high MRD negativity among responders in both settings (75.8% and 82.1%, respectively). In the public system, venetoclax-based therapy was associated with improved overall survival (OS) compared with the historical cohort treated with low-dose cytarabine or best supportive care (median 4.6 vs 1.0 months; p=0.001). Private venetoclax-treated patients achieved a median OS of 16.8 months, significantly longer than public venetoclax-treated patients (p=0.016). In the multivariable analysis restricted to venetoclax-treated patients, treatment center remained the only independent factor associated with OS. Venetoclax-based therapy was clinically active across distinct healthcare settings, and azole-adjusted dosing achieved comparable remission and MRD outcomes; however, persistent survival differences likely reflect the impact of systemic disparities in supportive care and infrastructure in LMICs.