FMS-Like Tyrosine Kinase 3 Inhibitors for the Treatment of Acute Myeloid Leukemia

Elli D Novatcheva; Yasmine Anouty; Ila Saunders; James K Mangan; Aaron M Goodman

doi:10.1016/j.clml.2021.09.002

FMS-Like Tyrosine Kinase 3 Inhibitors for the Treatment of Acute Myeloid Leukemia

Clin Lymphoma Myeloma Leuk. 2022 Mar;22(3):e161-e184. doi: 10.1016/j.clml.2021.09.002. Epub 2021 Sep 16.

Authors

Elli D Novatcheva¹, Yasmine Anouty², Ila Saunders³, James K Mangan⁴, Aaron M Goodman⁵

Affiliations

¹ University of California San Diego School of Medicine, La Jolla, CA.
² Department of Pharmacy, University of California San Diego Health, La Jolla, CA.
³ Department of Pharmacy, University of California San Diego Health, La Jolla, CA; UC San Diego Skaggs School of Pharmacy & Pharmaceutical Sciences, La Jolla, CA.
⁴ Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA.
⁵ Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA. Electronic address: a1goodman@ucsd.edu.

PMID: 34649791
DOI: 10.1016/j.clml.2021.09.002

Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia of adults, with a five-year survival that remains poor (approximately 25%). Knowledge and understanding of AML genomics have expanded tremendously over the past decade and are now included in AML prognostication and treatment decisions. FMS-like tyrosine kinase 3 (FLT3) is a Class III receptor tyrosine kinase (RTK) expressed primarily in the cell membranes of early hematopoietic progenitor cells, found in 28% of all patients with AML. FLT3 is the second most frequent mutation in adult AML following Nuclear-cytoplasmic shuttling phosphoprotein (NPM1), which is found in 50% of cases.¹ FLT3 inhibitors are promising new molecular therapeutics increasingly becoming standard of care for both newly diagnosed and relapsed/refractory FLT3 positive AML. This review will focus on the clinical trials/evidence, similarities, differences, clinical toxicities, and drug interactions relevant to treating clinicians as pertains to 5 FLT3-inhibitors: midostaurin, sorafenib, gilteritinib, crenolanib, and quizartinib.

Keywords: AML; Crenolanib; FLT3-ITD; FLT3-TKD; Gilteritinib; Midostaurin; Quizartinib; Sorafenib.

Publication types

Review

MeSH terms

Antineoplastic Agents* / pharmacology
Antineoplastic Agents* / therapeutic use
Humans
Leukemia, Myeloid, Acute* / therapy
Mutation
Protein Kinase Inhibitors / adverse effects
Sorafenib / therapeutic use
fms-Like Tyrosine Kinase 3 / genetics

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Sorafenib
fms-Like Tyrosine Kinase 3