Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation

Cancer. 2018 May 1;124(9):1954-1963. doi: 10.1002/cncr.31295. Epub 2018 Mar 6.

Abstract

Background: The objective of this study was to evaluate the effect of sorafenib on the outcomes of patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: A total of 144 patients with FLT3-ITD AML undergoing allo-HSCT between January 2012 and December 2015 were enrolled in this study. Depending on whether they were receiving sorafenib before transplantation or sorafenib maintenance after transplantation, patients were divided into 4 groups: patients receiving sorafenib before transplantation (group A; n = 36), patients receiving sorafenib after transplantation (group B; n = 32), patients receiving sorafenib both before and after transplantation (group C; n = 26), and patients receiving sorafenib neither before nor after transplantation (group D; n = 50). Outcomes were compared among these groups.

Results: The 3-year relapse rates were 22.2%, 18.8%, 15.8%, and 46.1% for groups A, B, C, and D, respectively (P = .006). The 3-year overall survival (OS) rates were 74.9%, 78.1%, 84.6%, and 50.9%, respectively (P = .023), and the 3-year leukemia-free survival (LFS) rates were 69.4%, 78.1%, 80.4%, and 34.8%, respectively (P < .001). The relapse rate was higher and the LFS was shorter in group D versus groups A, B, and C. The OS in group D was shorter than the OS in group C but was similar to the OS in groups A and B. A multivariate analysis revealed that sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application were protective factors for a lower relapse rate (hazard ratios [HRs], 0.436 [P = .048], 0.431 [P = .046], and 0.173 [P = .002], respectively) and longer LFS (HRs, 0.322 [P = .010], 0.343 [P = .014], and 0.187 [P = .001], respectively).

Conclusions: Sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application all could improve the outcomes for patients with FLT3-ITD AML. Further study is needed to determine whether the use of sorafenib both before and after transplantation might be ideal. Cancer 2018;124:1954-63. © 2018 American Cancer Society.

Keywords: FMS-like tyrosine kinase 3; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; internal tandem duplication; outcomes; sorafenib.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Combined Modality Therapy / methods
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gain of Function Mutation
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / prevention & control
  • Protein Domains / genetics
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Remission Induction / methods
  • Retrospective Studies
  • Segmental Duplications, Genomic / genetics
  • Sorafenib / pharmacology
  • Sorafenib / therapeutic use*
  • Survival Rate
  • Tandem Repeat Sequences / genetics
  • Transplantation, Homologous
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Protein Kinase Inhibitors
  • Sorafenib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3