A review of FDA-approved acute myeloid leukemia therapies beyond '7 + 3'

Expert Rev Hematol. 2021 Feb;14(2):185-197. doi: 10.1080/17474086.2021.1875814. Epub 2021 Jan 19.

Abstract

Introduction: The standard anthracycline and cytarabine-based chemotherapy for acute myeloid leukemia (AML) has changed relatively little since the 1970s and produces unsatisfactory outcomes in many patients. In the past two decades, a better understanding of the pathophysiology and heterogeneity of this disease has led to promising new therapies, resulting in a flurry of new drug approvals.Areas covered: The MEDLINE database, ClinicalTrials.gov and conference proceedings were reviewed for the most salient literature concerning FDA-approved drugs for AML beyond standard chemotherapy: gemtuzumab ozogamicin, hypomethylating agents, Fms-like tyrosine kinase 3 (FLT3) inhibitors, isocitrate dehydrogenase (IDH) inhibitors, venetoclax, liposomal cytarabine and daunorubicin (CPX-351), and hedgehog pathway inhibitors. Key evidence for their efficacy is discussed. For each drug category, indications, typical usage and responses, major toxicities, and future directions for research are highlighted.Expert opinion: The treatment paradigm for AML is rapidly evolving. Promising new drugs targeting driver mutations have improved outcomes in specific AML subgroups. In parallel, advances in low-intensity therapies have allowed patients unfit for standard induction chemotherapy to achieve meaningful disease control. Further work is ongoing to identify synergistic drug combinations as well as optimal treatment selection guided by individual patient and disease features.

Keywords: Acute myeloid leukemia; cpx-351; flt3 inhibitors; gemtuzumab ozogamicin; glasdegib; hypomethylating agents; idh inhibitors; low-intensity therapy; molecular targeted therapy; venetoclax.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Drug Approval
  • Gemtuzumab
  • Hedgehog Proteins / therapeutic use
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics

Substances

  • Antineoplastic Agents
  • Hedgehog Proteins
  • Gemtuzumab