Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia

• DOI: 10.1038/s41408-020-0318-1
• Publication Date: 2020-05-04T17:04:26Z
• Authors: Iman Abou Dalle; Ahmad Ghorab; Keyur Patel; Xuemei Wang; Hyunsoo Hwang; Jorge Cortes; Ghayas C. Issa; Fevzi Yalniz; Koji Sasaki; Dai Chihara; Allyson Price; Tapan Kadia; Naveen Pemmaraju; Naval Daver; Courtney DiNardo; Farhad Ravandi; Hagop M. Kantarjian; Gautam Borthakur
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Adolescent; Middle Aged; Prognosis; Survival Analysis; Article; 3. Good health; Cytogenetics; Leukemia, Myeloid, Acute; Young Adult; 03 medical and health sciences; Treatment Outcome; fms-Like Tyrosine Kinase 3; Mutation; Humans; Female; Nucleophosmin; Protein Kinase Inhibitors; Alleles; Aged

Abstract FLT3 -ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). diversity can further influence clinical outcomes. Addition of inhibitors to standard chemotherapy has improved OS. The aim this study is evaluate the prognostic impact and identify predictors efficacy inhibitors. We reviewed prospectively collected data from 395 patients mutant AML. 156 (39%) received combined either high or low intensity chemotherapy. There was no statistically significant difference outcomes among treated based on numerical variation ( p = 0.85), mutation length 0.67). Overall, addition inhibitor intensive an OS (HR 0.35, 95% CI: 0.24–0.5, 0.0005), but not combination lower 0.98, 95%CI: 0.7–1.36, 0.85). A differential effect more pronounced younger allelic ratio ≥0.5 0.41, 0.25–0.66, < 0.001), single ITD 0.55, 0.34–0.88, 0.01), diploid cytogenetics 0.52, 0.35–0.76, NPM1 co-mutation 0.19–0.67, 0.001). Our analysis identifies diverse related variables inhibitor.