Refining AML Treatment: The Role of Genetics in Response and Resistance Evaluation to New Agents

SIMPLE SUMMARY: Acute myeloid leukemia (AML) is an aggressive cancer of the hematopoietic system. At present, we know that AML is heterogeneous and varies from one patient to another, often characterized by specific changes in the DNA (mutations). Likewise, we know that the mutational landscape of the disease predicts its response to certain therapies and that it can change under the influence of therapy. Since 2017, the number of potential drugs intended to treat AML has substantially increased and so has our knowledge about the role of certain mutations in the prediction of disease response, relapse and resistance. In this article, we review the current state of knowledge of genetic aberrations with respect to clinical decision making. ABSTRACT: The number of treatment options for acute myeloid leukemia (AML) has greatly increased since 2017. This development is paralleled by the broad implantation of genetic profiling as an integral part of clinical studies, enabling us to characterize mutation–response, mutation–non-response, or mutation–relapse patterns. The aim of this review is to provide a concise overview of the current state of knowledge with respect to newly approved AML treatment options and the association of response, relapse and resistance with genetic alterations. Specifically, we will highlight current genetic data regarding FLT3 inhibitors, IDH inhibitors, hypomethylating agents (HMA), the BCL-2 inhibitor venetoclax (VEN), the anti-CD33 antibody conjugate gemtuzumab ozogamicin (GO) and the liposomal dual drug CPX-351.