TY - JOUR
T1 - Prognostic significance of baseline FLT3-ITD mutant allele level in acute myeloid leukemia treated with intensive chemotherapy with/without sorafenib
AU - Yalniz, Fevzi
AU - Abou Dalle, Iman
AU - Kantarjian, Hagop
AU - Borthakur, Gautam
AU - Kadia, Tapan
AU - Patel, Keyur
AU - Loghavi, Sanam
AU - Garcia-Manero, Guillermo
AU - Sasaki, Koji
AU - Daver, Naval
AU - DiNardo, Courtney
AU - Pemmaraju, Naveen
AU - Short, Nicholas J.
AU - Yilmaz, Musa
AU - Bose, Prithviraj
AU - Naqvi, Kiran
AU - Pierce, Sherry
AU - Nogueras González, Graciela M.
AU - Konopleva, Marina
AU - Andreeff, Michael
AU - Cortes, Jorge
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/9
Y1 - 2019/9
N2 - Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 gene (FLT3) confer a poor prognosis in adult AML. Studies have reported that a higher mutant allelic burden is associated with a worse prognosis. Adult patients with FLT3-ITD mutated AML treated at our institution were identified. Patients were assigned into 2 groups; patients who received idarubicin and cytarabine (IA, group one) containing induction, and who received sorafenib in addition to IA containing regimens at induction (group two). The optimal FLT3-ITD mutant allele cut-off was defined as the cut-off to divide the whole cohort with the highest statistical significance. A total of 183 patients including 104 (57%) in group one and 79 (43%) in group two were identified. The complete remission (CR)/CR with incomplete hematologic recovery (CRi) for group one and group two were 85% and 99%, respectively (P =.004). The median relapse free survival (RFS) for group one and two were 12 and 45 months, respectively (P =.02). The median overall survival (mOS) was 17 months in group one, and has not been reached in group two (P =.008). The optimal FLT3-ITD mutant allele cut-off for OS was 6.9% in group one, there was no optimal cut-off in group two. On multivariate analysis, poor performance status (PS) (P =.003), sorafenib (P =.01), and presenting white blood cells (WBC) (P <.001) were independent predictors of OS. Higher FLT3-ITD allele burden is associated with a worse outcome in patients treated with IA-based chemotherapy. Addition of sorafenib to chemotherapy not only nullifies the negative prognostic impact of higher allele burden, but also improves outcome of FLT3-ITD mutated AML patients regardless of the allele burden.
AB - Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 gene (FLT3) confer a poor prognosis in adult AML. Studies have reported that a higher mutant allelic burden is associated with a worse prognosis. Adult patients with FLT3-ITD mutated AML treated at our institution were identified. Patients were assigned into 2 groups; patients who received idarubicin and cytarabine (IA, group one) containing induction, and who received sorafenib in addition to IA containing regimens at induction (group two). The optimal FLT3-ITD mutant allele cut-off was defined as the cut-off to divide the whole cohort with the highest statistical significance. A total of 183 patients including 104 (57%) in group one and 79 (43%) in group two were identified. The complete remission (CR)/CR with incomplete hematologic recovery (CRi) for group one and group two were 85% and 99%, respectively (P =.004). The median relapse free survival (RFS) for group one and two were 12 and 45 months, respectively (P =.02). The median overall survival (mOS) was 17 months in group one, and has not been reached in group two (P =.008). The optimal FLT3-ITD mutant allele cut-off for OS was 6.9% in group one, there was no optimal cut-off in group two. On multivariate analysis, poor performance status (PS) (P =.003), sorafenib (P =.01), and presenting white blood cells (WBC) (P <.001) were independent predictors of OS. Higher FLT3-ITD allele burden is associated with a worse outcome in patients treated with IA-based chemotherapy. Addition of sorafenib to chemotherapy not only nullifies the negative prognostic impact of higher allele burden, but also improves outcome of FLT3-ITD mutated AML patients regardless of the allele burden.
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U2 - 10.1002/ajh.25553
DO - 10.1002/ajh.25553
M3 - Article
C2 - 31237017
AN - SCOPUS:85068085169
SN - 0361-8609
VL - 94
SP - 984
EP - 991
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 9
ER -