Real-world clinical outcomes of newly diagnosed AML unfit for intensive chemotherapy treated with venetoclax and azacitidine: does it depend on the number of days of venetoclax administration?

 Jozef Lukáš, Balázs Gálffy, Stanislava Fliegová, Zuzana Sninská, Ľubica Harvanová, Katarína Slezáková, Ladislav Sopko

Abstract:

Until 2020, patients with acute myeloid leukemia (AML) who were not suitable for intensive treatment were mostly limited to symptomatic and palliative care, or to low-intensity regimens including low-dose cytosine-arabinoside (ARA-C) and azacitidine (AZA) monotherapy, which didn't bring much benefit. The situation changed with the arrival of venetoclax, a Bcl-2 inhibitor that causes leukemic cells to rapidly undergo apoptosis. The aim of our retrospective study was to summarize the treatment outcomes of all newly diagnosed patients with AML, unsuitable for intensive chemotherapy, treated with a combination of venetoclax and AZA at the Department of Hematology and Transfusion Medicine, University Hospital in Bratislava from January 1, 2021, to December 31, 2025. A total of 108 patients underwent treatment with a median follow-up of 35.9 months; median age was 69.5 years (47-84 years) and median number of cycles 3 (1-34). Induction mortality rate was 7.4%, and tumor lysis syndrome occurred in 4.5%. The overall response rate, which included the number of complete remissions, complete remissions with incomplete hematopoietic recovery, and morphologically leukemia-free status (CR/CRi/MLFS), was 64%, the median overall survival was 9 months, and disease-free survival was 8 months. As of December 31, 2025, 23 patients are alive and 85 have died. The main cause of death was the progression of the disease. The main contribution of our study is the finding that shortening the duration of venetoclax treatment maintains efficacy. There was no significant difference in remission rate achieved or in overall survival based on the number of days of venetoclax administration (< 14 vs. 14 vs. 21 vs. 28 days). The combination of AZA and venetoclax in AML has proven to be highly effective in inducing complete remission, usually immediately after the first cycle. Unfortunately, remission is not long-lasting, relapses are frequent, and the median overall survival in real-world data is 7.9 to 13.6 months.