New Therapeutic Strategies for Adult Acute Myeloid Leukemia

SIMPLE SUMMARY: For almost 40 years, the combination of anthracyclines and cytarabine, called 3 + 7, has been the standard of induction chemotherapy for the treatment of acute myeloid leukemia (AML). However, with the advent of new drugs in recent years, it has become possible to improve the prognosis of patients with AML harboring certain genetic mutations. Additionally, immunotherapies and therapies targeting cell-surface antigens, which are highly expressed in AML, are emerging. Herein, we review new therapeutic strategies for AML that are evolving with the introduction of these drugs. ABSTRACT: Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy. Chromosomal and genetic analyses are important for the diagnosis and prognosis of AML. Some patients experience relapse or have refractory disease, despite conventional cytotoxic chemotherapies and allogeneic transplantation, and a variety of new agents and treatment strategies have emerged. After over 20 years during which no new drugs became available for the treatment of AML, the CD33-targeting antibody–drug conjugate gemtuzumab ozogamicin was developed. This is currently used in combination with standard chemotherapy or as a single agent. CPX-351, a liposomal formulation containing daunorubicin and cytarabine, has become one of the standard treatments for secondary AML in the elderly. FMS-like tyrosine kinase 3 (FLT3) inhibitors and isocitrate dehydrogenase 1/2 (IDH 1/2) inhibitors are mainly used for AML patients with actionable mutations. In addition to hypomethylating agents and venetoclax, a B-cell lymphoma-2 inhibitor is used in frail patients with newly diagnosed AML. Recently, tumor protein p53 inhibitors, cyclin-dependent kinase inhibitors, and NEDD8 E1-activating enzyme inhibitors have been gaining attention, and a suitable strategy for the use of these drugs is required. Antibody drugs targeting cell-surface markers and immunotherapies, such as antibody–drug conjugates and chimeric antigen receptor T-cell therapy, have also been developed for AML.