The safety profile of FLT3 inhibitors in the treatment of newly diagnosed or relapsed/refractory acute myeloid leukemia

Expert Opin Drug Saf. 2021 Jul;20(7):791-799. doi: 10.1080/14740338.2021.1913120. Epub 2021 Apr 14.

Abstract

Introduction: FLT3 inhibitors are important drugs in the therapy of FLT3 positive acute myeloid leukemia (AML). Midostaurin was registered in combination with chemotherapy to treat newly diagnosed AML. Gilteritinib and quizartinib demonstrate effectiveness in a randomized trial in relapsed/refractory AML. Several promising FLT3 inhibitors are being evaluated in clinical research.

Areas covered: This review will report the safety of FLT3 inhibitors that are registered for acute myeloid leukemia induction and rescue therapy.

Expert opinion: In the near future, it is possible that all the FLT3 positive non M3-AML patients will receive a FLT3 inhibitor. Therapy adherence and strategies to mitigate adverse events must be pursued. The treatment with FLT3 inhibitors may be optimized in terms of toxicities with a rational evaluation of antifungal prophylaxis and concomitant therapy, cardiology monitoring, and keeping in mind rare adverse events. Future studies on unfit patients, special populations, and maintenance settings are warranted, together with post-market studies and real-life experiences. Whenever new FLT3 inhibitors will come to the clinic, we could face a scenario in which profound knowledge of effectiveness, toxicities, and off-target effects will be relevant to choose the best drug for each patient.

Keywords: Acute myeloid leukemia (AML); flt3; gilteritinib; midostaurin; quizartinib; safety; tyrosine kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Aniline Compounds / administration & dosage
  • Aniline Compounds / adverse effects
  • Aniline Compounds / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Benzothiazoles / administration & dosage
  • Benzothiazoles / adverse effects
  • Benzothiazoles / pharmacology
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / pathology
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacology
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Pyrazines / pharmacology
  • Randomized Controlled Trials as Topic
  • Staurosporine / administration & dosage
  • Staurosporine / adverse effects
  • Staurosporine / analogs & derivatives
  • Staurosporine / pharmacology
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Benzothiazoles
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyrazines
  • gilteritinib
  • quizartinib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Staurosporine
  • midostaurin