A User's Guide to Novel Therapies for Acute Myeloid Leukemia.

Few diseases have been marked by a 40-year period of stagnation with regard to therapeutic advances and United States Food and Drug Administration (FDA) approvals, as has been the case for acute myeloid leukemia (AML). Cytarabine and anthracyclines were introduced for the treatment of AML in the 1970s, and in the ensuing 4 decades, the pharmacologic pipeline has experienced a standstill. The absence of FDA approvals in AML is not a reflection of the lack of understanding of the disease biology. The field has seen major advances from the standpoint of stem cell biology and clonal evolution, and the field has also seen some therapeutic advances, but these therapeutic advances have arisen from optimization of the same traditional cytotoxic chemotherapeutics rather than the development of novel therapies. The year 2017 marked a turning point with regard to FDA approvals. This review summarizes the salient clinical trials that led to the approval of 8 novel agents in AML in the past 2 years. For these agents, the clinical activity is often defined by specific molecular aberrations or metabolic features of AML cells. We also emphasize the principles of management of AML in the current era of genomic medicine, with a focus on considerations for targeting mutation-specific vulnerabilities in select patients. This review also highlights unique challenges to the use of novel agents in 2020, including considerations of curative potential with regards to bridging to allogeneic stem cell transplant, tolerability, financial toxicities, and microenvironmental hurdles. Finally, we discuss prospects on future immunotherapeutic investigational agents in the pharmacologic pipeline.