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

• Published in: Cancer Vol. 124; no. 9; pp. 1954 - 1963
• Main Authors: Xuan, Li, Wang, Yu, Huang, Fen, Jiang, Erlie, Deng, Lan, Wu, Bingyi, Fan, Zhiping, Liang, Xinquan, Xu, Na, Ye, Jieyu, Lin, Ren, Yin, Changxin, Zhang, Yuanyuan, Sun, Jing, Han, Mingzhe, Huang, Xiaojun, Liu, Qifa
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2018
• Subjects: Acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; Cancer; FMS‐like tyrosine kinase 3; Hematopoietic stem cells; Inhibitor drugs; internal tandem duplication; Leukemia; Maintenance; Multivariate analysis; Myeloid leukemia; Oncology; outcomes; Patients; Protein-tyrosine kinase; sorafenib; Stem cell transplantation; Stem cells; Survival; Targeted cancer therapy; Transplantation; Tyrosine; FMS-like tyrosine kinase 3; acute myeloid leukemia; sorafenib; internal tandem duplication; outcomes; allogeneic hematopoietic stem cell transplantation
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.31295

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. Sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application all can improve the outcomes for patients with acute myeloid leukemia with FMS‐like tyrosine kinase 3–internal tandem duplication. Further study is needed to determine whether the use of sorafenib both before and after transplantation might be ideal.