Long-term follow-up of oral decitabine/cedazuridine plus venetoclax for older or unfit patients with newly diagnosed acute myeloid leukemia

Abstract

Oral decitabine/cedazuridine plus venetoclax offers a fully oral regimen for older or unfit patients with acute myeloid leukemia (AML). We previously reported outcomes from a phase II study; here we present extended follow-up of the frontline cohort. In this single-center phase II study, adults with AML ineligible for intensive induction received oral decitabine/cedazuridine (35 mg/100 mg, days 1-5) plus venetoclax in 28-day cycles. This analysis included newly diagnosed (ND) AML. Endpoints included overall response rate (ORR), overall survival (OS), relapse-free survival (RFS), duration of response (DOR) and safety. Outcomes were compared between de novo and secondary AML. Between March 2021, and January 2026, 68 patients were treated, including 32 de novo and 36 secondary AML; median age was 79 years. The cohort was high risk, with >50% ECOG ≥2, less favorable genomics and 16% prior hypomethylating agents exposure. ORR was 75% in de novo AML and 58% in secondary AML. Among responders, MRD negativity was 58% and 56%. With median follow-up of 32 months, median OS was 12.7 months (95% CI, 9.1-20.3) vs 7.2 months (95% CI, 3.6-29.9) (P = 0.61). Median RFS was 9.2 months vs 11.7 months (P = 0.56). No statistically significant differences were observed in survival, relapse or non-relapse mortality. Oral decitabine/cedazuridine plus venetoclax is an effective oral treatment for older or unfit patients with ND AML. Response rates were higher in de novo AML, while survival outcomes were not statistically significant. These findings highlight the need for improved therapeutic strategies particularly in secondary AML.