TY - JOUR
T1 - Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3-internal tandem duplication mutation–positive acute myeloid leukemia
AU - Sasaki, Koji
AU - Kantarjian, Hagop M.
AU - Kadia, Tapan
AU - Patel, Keyur
AU - Loghavi, Sanam
AU - Garcia-Manero, Guillermo
AU - Jabbour, Elias J.
AU - DiNardo, Courtney
AU - Pemmaraju, Naveen
AU - Daver, Naval
AU - Dalle, Iman Abou
AU - Short, Nicholas
AU - Yilmaz, Musa
AU - Bose, Prithviraj
AU - Naqvi, Kiran
AU - Pierce, Sherry
AU - Yalniz, Fevzi
AU - Cortes, Jorge E.
AU - Ravandi, Farhad
N1 - Publisher Copyright:
© 2019 American Cancer Society
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background: The addition of midostaurin to induction chemotherapy improves survival in younger patients with newly diagnosed, FLT3–mutated acute myeloid leukemia (AML). Sorafenib is a potent multikinase inhibitor with efficacy when given as monotherapy. The authors investigated whether the addition of sorafenib to intensive induction chemotherapy improves outcomes in patients with FLT3-internal tandem duplication (ITD)–mutated AML. Methods: In total, 183 patients who were newly diagnosed with FLT3-ITD–mutated AML between February 2001 and December 2017 were identified. Of these, 79 patients (43%) underwent intensive chemotherapy with the addition of sorafenib, and 104 (57%) received intensive chemotherapy alone. Propensity score matching identified 42 patients in each cohort. Results: The overall response rate was 98% in the sorafenib cohort and 83% in the intensive chemotherapy cohort (P =.057). The median follow-up was 54 months. The median event-free survival was 35 months in the sorafenib cohort and 8 months in the intensive chemotherapy cohort (P =.019), and the median overall survival was 42 and 13 months, respectively (P =.026). With censoring at the time of allogeneic stem cell transplantation, the median event-free survival was 31 and 8 months in the sorafenib and intensive therapy cohorts, respectively (P =.031), and the median overall survival was not reached and 10 months, respectively (P =.001). Multivariate Cox proportional hazards models confirmed that treatment with sorafenib was a favorable prognostic factor (P =.009; hazard ratio, 0.558; 95% CI, 0.360-0.865). Conclusions: The addition of sorafenib improves survival in patients with FLT3-ITD–mutated AML regardless of whether they undergo allogeneic stem cell transplantation.
AB - Background: The addition of midostaurin to induction chemotherapy improves survival in younger patients with newly diagnosed, FLT3–mutated acute myeloid leukemia (AML). Sorafenib is a potent multikinase inhibitor with efficacy when given as monotherapy. The authors investigated whether the addition of sorafenib to intensive induction chemotherapy improves outcomes in patients with FLT3-internal tandem duplication (ITD)–mutated AML. Methods: In total, 183 patients who were newly diagnosed with FLT3-ITD–mutated AML between February 2001 and December 2017 were identified. Of these, 79 patients (43%) underwent intensive chemotherapy with the addition of sorafenib, and 104 (57%) received intensive chemotherapy alone. Propensity score matching identified 42 patients in each cohort. Results: The overall response rate was 98% in the sorafenib cohort and 83% in the intensive chemotherapy cohort (P =.057). The median follow-up was 54 months. The median event-free survival was 35 months in the sorafenib cohort and 8 months in the intensive chemotherapy cohort (P =.019), and the median overall survival was 42 and 13 months, respectively (P =.026). With censoring at the time of allogeneic stem cell transplantation, the median event-free survival was 31 and 8 months in the sorafenib and intensive therapy cohorts, respectively (P =.031), and the median overall survival was not reached and 10 months, respectively (P =.001). Multivariate Cox proportional hazards models confirmed that treatment with sorafenib was a favorable prognostic factor (P =.009; hazard ratio, 0.558; 95% CI, 0.360-0.865). Conclusions: The addition of sorafenib improves survival in patients with FLT3-ITD–mutated AML regardless of whether they undergo allogeneic stem cell transplantation.
KW - FLT3-internal tandem duplication (FLT3-ITD)
KW - acute myeloid leukemia
KW - allogeneic stem cell transplantation
KW - induction chemotherapy
KW - sorafenib
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U2 - 10.1002/cncr.32387
DO - 10.1002/cncr.32387
M3 - Article
C2 - 31310323
AN - SCOPUS:85069656027
SN - 0008-543X
VL - 125
SP - 3755
EP - 3766
JO - Cancer
JF - Cancer
IS - 21
ER -