基于二代测序技术分析骨髓纤维化患者基因突变对芦可替尼疗效的影响

OBJECTIVE: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis（MF）. METHODS: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing（NGS）technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. RESULTS: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis（PMF）, 9 cases of bone marrow fibrosis（ppv-mf）after polycythemia vera, and 11 cases of bone marrow fibrosis（PET-MF）after primary thrombocytosis（ET）. ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50（89.29％）carried driver mutations, 22（39.29％）carried ≥3 mutations, and 29（51.79％）carried high-risk mutations（HMR）. ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen（P＝0.001, P<0.001）, but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations（P＝0.007, P＝0.042）. ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR（t＝10.471, P＝0.034）, and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations（P<0.001, P＝0.001）. ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF［ASXL1: 360（55-1270）d vs 440（55–1268）d, z＝−3.115, P＝0.002; EZH2: 327（55–975）d vs 404（50–1270）d, z＝−3.219, P＝0.001］, and significantly shorter PFS compared to non-carriers［ASXL1: 457（50–1331）d vs 574（55–1437）d, z＝−3.219, P＝0.001）; 428（55–1331）d vs 505（55–1437）d, z＝−2.576, P＝0.008］. CONCLUSION: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.