The potential of triplet combination therapies for patients with FLT3-ITD -mutated acute myeloid leukemia

Expert Rev Hematol. 2024 Jun;17(6):241-253. doi: 10.1080/17474086.2024.2356258. Epub 2024 May 20.

Abstract

Introduction: Acute myeloid leukemia (AML) encompasses a heterogeneous group of aggressive myeloid malignancies, where FMS-like tyrosine kinase 3 (FLT3) mutations are prevalent, accounting for approximately 25-30% of adult patients. The presence of this mutation is related to a dismal prognosis and high relapse rates. In the lasts years many FLT3 inhibitors have been developed.

Areas covered: This review provides a comprehensive overview of FLT3mut AML, summarizing the state of art of current treatment and available data about combination strategies including an FLT3 inhibitor.

Expert opinion: In addition, the review discusses the emergence of drug resistance and the need for a nuanced approaches in treating patients who are ineligible for or resistant to intensive chemotherapy. Specifically, it explores the historical context of FLT3 inhibitors (FLT3Is) and their impact on treatment outcomes, emphasizing the pivotal role of midostaurin, as well as gilteritinib and quizartinib, and providing detailed insights into ongoing trials exploring the safety and efficacy of novel triplet combinations involving FLT3Is in different AML settings.

Keywords: Acute myeloid leukemia; FLT3 inhibition; FLT3 mutation; FLT3-ITD; triplet therapy in AML.

Publication types

  • Review

MeSH terms

  • Aniline Compounds
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Mutation*
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrazines
  • Staurosporine / analogs & derivatives
  • Staurosporine / therapeutic use
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3* / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3* / genetics

Substances

  • fms-Like Tyrosine Kinase 3
  • FLT3 protein, human
  • Protein Kinase Inhibitors
  • gilteritinib
  • midostaurin
  • Staurosporine
  • Aniline Compounds
  • Pyrazines