Venetoclax in Acute Myeloid Leukemia

Abstract

Background: Substantial progress in the therapeutic arsenal used to treat acute myeloid leukemia became possible in the last decade, as a result of advances in gene editing and descriptive and functional genomics.

Objective: The aim of this study is to analyze the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia.

Methods: A mini-review was achieved using the articles published in PubMed and Web of Science in the last year, prior to 05.05.2021, which were searched using the terms "acute myeloid leukemia" and "venetoclax" and the new patents published in this field.

Results: BCL-2 inhibitors administered in monotherapy are active against acute myeloid leukemia cells, but their efficacy is partially limited because they do not target other antiapoptotic proteins and venetoclax induced overexpression of the other antiapoptotic molecules. Venetoclax-based combinations (including those with hypomethylating agents) were able to improve outcomes for older patients with acute myeloid leukemia, including both remission rates and overall survival. Other drugs used in combination with venetoclax include: FLT3 inhibitors, IDH2 inhibitors, chidamide, ibrutinib, lapatinib, mivebresib, triptolide, metabolic inhibitors, nucleoside analogs, and classical chemotherapeutics. Both the mechanisms of venetoclax resistance and the ways to overcome it, as well as the adverse effects of venetoclax are analyzed.

Conclusion: The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.

Keywords: Acute myeloid leukemia; BCL-2; apoptosis; hypomethylating agent; minimal residual disease; myelodysplastic syndrome; tumor lysis syndrome; venetoclax.