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

Journal: Clinical lymphoma, myeloma & leukemia 2022;22(3):e161-e184

PMID: 34649791

Free Full Text on Elsevier Science View on PubMed

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. 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.

Address: University of California San Diego School of Medicine, La Jolla, CA.; Department of Pharmacy, University of California San Diego Health, La Jolla, CA.; Department of Pharmacy, University of California San Diego Health, La Jolla, CA; UC San Diego Skaggs School of Pharmacy & Pharmaceutical Sciences, La Jolla, CA.; Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA.; Department of Medicine, Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA. Electronic address: [email protected].

DOI: 10.1016/j.clml.2021.09.002