An overview of novel therapies in advanced clinical testing for acute myeloid leukemia

The past decade has seen a sea change in the AML landscape with vastly improved cognizance of molecular pathogenesis, clonal evolution, and importance of measurable residual disease. Since 2017, the therapeutic armamentarium of AML has considerably expanded with the approval of midostaurin, enasidenib, ivosidenib, gilteritinib, and venetoclax in combination with hypomethylating agents and others. Nevertheless, relapse and treatment refractoriness remain the insurmountable challenges in AML therapy. This has galvanized the leukemic research community leading to the discovery and development of agents that specifically target gene mutations, molecularly agnostic therapies that exploit immune environment, apoptotic pathways, leukemic cell surface antigens and so forth.

This article provides an overview of the pathophysiology of AML in the context of non-cellular immune and molecularly targeted and agnostic therapies that are in clinical trial development in AML.

Ever growing understanding of the molecular pathogenesis and metabolomics in AML has allowed the researchers to identify targets directed at specific genes and metabolic pathways. As a result, AML therapy is constantly evolving and so are the escape mechanisms leading to disease relapse. Therefore, it is of paramount importance to sequentially evaluate the patient during AML treatment and intervene at the right time.