The impact of FLT3 mutations on treatment response and survival in Chinese de novo AML patients

ABSTRACT

Objective: Two distinct forms of FMS-like tyrosine kinase 3 (FLT3) mutations, internal tandem duplication (ITD) in the juxtamembrane domain and point mutation within the activation loop of the tyrosine kinase domain (TKD), have been identified in considerable number of patients with AML. This study was aimed to analyze the impacts of these mutations on clinical outcomes, and assess the efficacy of different therapeutic regimens (allo-HSCT, sorafenib, or conventional chemotherapy) for AML patients with FLT3 mutations after the standard induction therapy.

Materials and methods: We analyzed DNA samples from 158 consecutive de novo AML patients (18–60 years, excluding APL) with FLT3 mutations between July 2010 and October 2015.

Results: We found that AML patients with FLT3-TKD mutations have more favorable clinical outcomes than those with FLT3-ITD mutations. We also found that allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients (p < 0.001, p = 0.071). However, compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients. Further study on a large scale is still recommended.

Conclusions: FLT3-TKD-mutated AML patients have more favorable clinical outcomes than those with FLT3-ITD mutations. Allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients. Compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients.

KEYWORDS:

• Gene mutation
• FLT3-ITD
• FLT3-TKD
• prognosis
• AML

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the science and technology key project on clinical medicine of Jiangsu province (Grant No. BL2014038), the outstanding medical academic leader program of Jiangsu province (Grant No. LJ201138), the National Natural Science Foundation of China (Grant Nos. 81470296, 81400112, 81671549), Jiangsu Provincial Medical Youth Talent Program (Grant No. QNRC2016719, QNRC2016771), a C class sponsored project of Jiangsu provincial Six Talent Peaks (Grant No. 2016-WSN-123).