Tailoring intensive and less-intensive treatment in acute myeloid leukemia

After decades of therapeutic inertia, the treatment of acute myeloid leukemia (AML) has seen remarkable improvements over the past ten years. Scientific discoveries have substantially enhanced the understanding of AML disease biology. The improved knowledge about leukemic transformation and disease mechanisms in this heterogeneous group of aggressive blood cancers has resulted in enhanced biologically defined risk prognostication and the development of novel targeted therapeutic agents. Many of these mechanism-based therapeutics have entered clinical development, with some getting approval for the treatment of specific genetically defined AML subgroups in patients fit or unfit for intensive chemotherapy-based treatment. As a result, the European LeukemiaNet (ELN) expert panel has established a distinct genetic risk stratification for AML patients undergoing less-intensive treatment, which incorporates targeted drugs (ELN 2024). The ELN 2022 risk categories, designed for predicting outcomes following intensive chemotherapy, did not adequately assess responses to these new regimens. In this review, we discuss the current state-of-the-art approaches in both intensive and less-intensive front-line treatments for AML, highlighting the most promising therapeutic innovations.