Practical tips for managing FLT3 mutated acute myeloid leukemia with midostaurin

Expert Rev Hematol. 2022 Mar;15(3):203-214. doi: 10.1080/17474086.2022.2054801. Epub 2022 Mar 25.

Abstract

Introduction: FLT3 inhibitors have been recently introduced as novel treatment targets in patients with FLT3-mutated acute myeloid leukemia (AML). Midostaurin is an oral multikinase inhibitor that targets multiple receptor tyrosine kinases including FLT3 and has been approved for the treatment of AML with FLT3 mutations in patients candidates for intensive chemotherapy. This article presents an updated overall overview of the use of midostaurin in clinical practice.

Areas covered: Tests and examinations to be performed before the use of midostaurin, antifungal and antimicrobial treatment, as well as antifungal and antimicrobial prophylaxis are discussed. Practical tips for the treatment of QTc interval prolongation and heart failure are also presented.

Expert opinion: Midostaurin is the first agent showing significant survival benefit when combined with chemotherapy in FLT3-mutated AML patients. Optimal use of midostaurin should be a priority, being essential to know the interactions with other drugs like strong CYP3A4 inhibitors or inducers, which are particularly used in the concomitant treatment of AML patients and may increase toxicity or decrease therapeutic benefit. The active role of hematologists and nursing teams is crucial to ensure patient adherence to midostaurin treatment and to minimize adverse effects by administrating the optimal dose for each situation.

Keywords: AML; CYP3A4; FLT3 mutation; expert opinion; midostaurin management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / therapeutic use
  • Antineoplastic Agents* / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Staurosporine / analogs & derivatives
  • Staurosporine / pharmacology
  • Staurosporine / therapeutic use
  • fms-Like Tyrosine Kinase 3 / genetics

Substances

  • Antifungal Agents
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Staurosporine
  • midostaurin