Advancing treatment of acute myeloid leukemia: the future of FLT3 inhibitors.
Expert Rev Anticancer Ther
; 19(3): 273-286, 2019 03.
Article
in En
| MEDLINE
| ID: mdl-30681373
ABSTRACT
INTRODUCTION:
Mutations of the FLT3 gene are among most common genetic abnormalities occurring in acute myeloid leukemia (AML) and are associated with dismal prognosis. Tremendous effort has been devoted to developing clinically effective FLT3 inhibitors. First generation inhibitors consisted of multi-kinase inhibitors (sorafenib, lestaurtinib, midostaurin), which blocked FLT3 as well as multiple other kinase receptors. The failure of these agents to induce durable responses led to the development of second generation FLT3 tyrosine kinase inhibitors (quizartinib, crenolinib, gilteritinib) exhibiting high potency and specificity for mutant FLT3 kinases and sustained in vivo FLT3 inhibition. These myriad FLT3 inhibitors possess diverse kinase inhibitory properties, toxicity profiles, and pharmacokinetics, which impact on their incorporation into therapeutic regimens. Areas covered This article reviews the medical literature on current and future FLT3 inhibitors for AML therapy. We provide algorithms for which kinase inhibitor should be utilized for different FLT3 mutations (ITD±TKD) and clinical scenarios (de novo, relapsed/refractory, fit vs. unfit) and discuss novel FLT3 targeted therapeutic approaches. Expert commentary Integration of clinically active FLT3 inhibitors into all stages of therapy for all individuals with FLT3 mutant AML promises to significantly improve outcomes for this poor prognosis disease.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Myeloid, Acute
/
Protein Kinase Inhibitors
/
Fms-Like Tyrosine Kinase 3
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Expert Rev Anticancer Ther
Journal subject:
NEOPLASIAS
/
TERAPEUTICA
Year:
2019
Document type:
Article
Affiliation country:
United States