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

Leuk Lymphoma. 2019 Jun;60(6):1354-1369. doi: 10.1080/10428194.2018.1546854. Epub 2019 Jan 17.

Abstract

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.

Keywords: inhibitor; Acute myelogenous leukemia; epigenetic therapy; future directions; novel therapies; targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Clinical Trials as Topic
  • Disease Management
  • Drug Approval
  • Drug Discovery
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / etiology
  • Molecular Targeted Therapy* / methods
  • Molecular Targeted Therapy* / trends
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor