TY - JOUR
T1 - 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
AU - Abou Dalle, Iman
AU - Ghorab, Ahmad
AU - Patel, Keyur
AU - Wang, Xuemei
AU - Hwang, Hyunsoo
AU - Cortes, Jorge
AU - Issa, Ghayas C.
AU - Yalniz, Fevzi
AU - Sasaki, Koji
AU - Chihara, Dai
AU - Price, Allyson
AU - Kadia, Tapan
AU - Pemmaraju, Naveen
AU - Daver, Naval
AU - DiNardo, Courtney
AU - Ravandi, Farhad
AU - Kantarjian, Hagop M.
AU - Borthakur, Gautam
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/5/1
Y1 - 2020/5/1
N2 - FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.36, p = 0.85). A differential effect of FLT3 inhibitor on OS was more pronounced in younger patients with FLT3 allelic ratio ≥0.5 (HR = 0.41, 95% CI: 0.25–0.66, p < 0.001), single ITD mutation (HR = 0.55, 95% CI: 0.34–0.88, p = 0.01), diploid cytogenetics (HR = 0.52, 95% CI: 0.35–0.76, p = 0.001), NPM1 co-mutation (HR = 0.35, 95% CI: 0.19–0.67, p = 0.001). Our analysis identifies predictors of survival among diverse FLT3 related variables in patients treated with FLT3 inhibitor.
AB - FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.36, p = 0.85). A differential effect of FLT3 inhibitor on OS was more pronounced in younger patients with FLT3 allelic ratio ≥0.5 (HR = 0.41, 95% CI: 0.25–0.66, p < 0.001), single ITD mutation (HR = 0.55, 95% CI: 0.34–0.88, p = 0.01), diploid cytogenetics (HR = 0.52, 95% CI: 0.35–0.76, p = 0.001), NPM1 co-mutation (HR = 0.35, 95% CI: 0.19–0.67, p = 0.001). Our analysis identifies predictors of survival among diverse FLT3 related variables in patients treated with FLT3 inhibitor.
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U2 - 10.1038/s41408-020-0318-1
DO - 10.1038/s41408-020-0318-1
M3 - Article
C2 - 32366841
AN - SCOPUS:85084235927
SN - 2044-5385
VL - 10
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 5
M1 - 48
ER -