An evaluation of venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine as therapy for acute myeloid leukemia

Abstract

Introduction: Older patients with acute myeloid leukemia (AML) ineligible for conventional chemotherapy have historically received low-intensity treatments, if any, and have had dismal outcomes. Recent phase III data have demonstrated significant efficacy of venetoclax-based combinations and have begun to address the unmet need in this patient population. As venetoclax-based combinations become increasingly used in the clinical setting, it is important to understand their development, current use, and future directions.

Areas covered: This review covers the clinical development of venetoclax-based combinations for the management of AML, and their current and future use. A search of PubMed and ashpublications.org using the keywords 'venetoclax', 'AML', and 'hypomethylating agents' as the search terms was undertaken to identify the most pertinent publications.

Expert opinion: While venetoclax-based combinations have shown excellent responses and improved survival in patients with untreated AML, further studies are required to understand how to expand on their frontline use, manage patients who fail venetoclax-based combinations, and their true efficacy in the relapsed/refractory setting. Management of AML with venetoclax-based combinations is expected to evolve over the next few years.

Keywords: Acute myeloid leukemia; aml; azacitidine; cytarabine; decitabine; hma; hypomethylating agent; ldac; venetoclax.

Figure 1:

HMA-VEN demonstrates synergistic activity against leukemic stem cells by inhibiting amino acid uptake and disrupting the tricarboxylic acid (TCA) cycle via inhibition of electron transport chain complex II, ultimately leading to cell death. Amino acids are represented in red circles.