Population pharmacokinetic (PopPK) and concentration-QTc analysis of quizartinib in patients (pts) with FLT3-ITD–positive relapsed/refractory (R/R) acute myeloid leukemia (AML)

Authors: Kang D, Ludwig EA, Jaworowicz DJ, Huang H, Fiedler-Kelly J, Cortes J, Ganguly S, Khaled S, Krämer A, Levis M, Martinelli G, Perl A, Russell N, Abutarif M, Choi Y, Kobayashi K, Mendell J, Yin O
Conference: European Hematology Association (EHA)
Keywords: Fms-related tyrosine kinase 3, Quizartinib
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background

• Fms-related tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells; signaling through FLT3 promotes their proliferation and differentiation. FLT3 is mutated in approximately 30% of patients with AML
• The FLT3–internal tandem duplication (ITD) mutation represents the most common type of FLT3 mutation and is associated with high relapse rates, decreased response to salvage therapy, and shorter overall survival (OS)
• Quizartinib is an oral, once-daily, highly potent and selective, next-generation, type II FLT3 inhibitor that has shown high clinical activity in patients with FLT3-ITD positive R/R AML
• Single-agent quizartinib demonstrated a clinically meaningful OS benefit in patients with R/R FLT3-ITD AML vs salvage chemotherapy, with a 24% reduction in the risk of death in the phase 3 QuANTUM-R (AC220-007) trial

European Hematology Association (EHA); June 13-16 2019, Amsterdam, Netherlands.

By D Kang, Elizabeth A Ludwig, David J Jaworowicz, Hannah Huang, Jill Fiedler-Kelly, J Cortes, S Ganguly, S Khaled, A Krämer, M Levis, G Martinelli, A Perl, N Russell, M Abutarif, Y Choi, K Kobayashi, J Mendell, O Yin