Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3-internal tandem duplication mutation–positive acute myeloid leukemia

Koji Sasaki, Hagop M. Kantarjian, Tapan Kadia, Keyur Patel, Sanam Loghavi, Guillermo Garcia-Manero, Elias J. Jabbour, Courtney DiNardo, Naveen Pemmaraju, Naval Daver, Iman Abou Dalle, Nicholas Short, Musa Yilmaz, Prithviraj Bose, Kiran Naqvi, Sherry Pierce, Fevzi Yalniz, Jorge E. Cortes, Farhad Ravandi

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4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3755-3766
Number of pages12
JournalCancer
Volume125
Issue number21
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

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Keywords

  • acute myeloid leukemia
  • allogeneic stem cell transplantation
  • FLT3-internal tandem duplication (FLT3-ITD)
  • induction chemotherapy
  • sorafenib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sasaki, K., Kantarjian, H. M., Kadia, T., Patel, K., Loghavi, S., Garcia-Manero, G., Jabbour, E. J., DiNardo, C., Pemmaraju, N., Daver, N., Dalle, I. A., Short, N., Yilmaz, M., Bose, P., Naqvi, K., Pierce, S., Yalniz, F., Cortes, J. E., & Ravandi, F. (2019). Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3-internal tandem duplication mutation–positive acute myeloid leukemia. Cancer, 125(21), 3755-3766. https://doi.org/10.1002/cncr.32387