Are we witnessing the start of a therapeutic revolution in acute myeloid leukemia?

The 5-year overall survival rate of AML patients remains 25-40%. The prognosis is even more dismal for older patients who are ineligible for intensive chemotherapy and patients with secondary or relapsed/refractory AML. In 2017, 4 new drugs were approved by the US Food and Drug Administration for AML treatment: The FLT3 inhibitor midostaurin, the isocitrate dehydrogenase (IDH)-2 inhibitor enasidenib, a liposomal formulation of cytarabine and daunorubicin (CPX-351), and the anti-CD33 antibody gemtuzumab ozogamicin. Additionally, the IDH1 inhibitor ivosidenib has received FDA approval in July 2018. However, all these drugs were approved in certain settings and/or for certain subsets of AML patients. Herein, we review the mechanisms of actions and preclinical data, highlight pivotal clinical trial data, and discuss future directions and challenges for further development of these 5 novel therapeutics. Finally, we briefly overview some of the highly promising agents that are currently in advanced stages of clinical development.