Effect of ruxolitinib on patients with primary myelofibrosis carrying non-driver mutations
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摘要: 目的 研究非驱动突变对芦可替尼治疗原发性骨髓纤维化(primary myelofibrosis，PMF)患者的疗效及影响。方法 回顾性分析2017年1月1日—2022年3月1日就诊于潍坊市人民医院血液科初诊的46例PMF患者的临床资料，探索非驱动突变与芦可替尼疗效的关系。结果 46例PMF患者中44例检测出突变，其中6例患者驱动基因检测为三阴型，2例患者未检测出任何基因突变。携带≥3个突变基因组的患者21例，< 3个突变基因组25例，对携带≥3个基因突变的PMF患者芦可替尼仍有较好的缩脾及改善体质性症状的效果(P=0.002，0.045)，与 < 3个突变组比较经芦可替尼治疗后缩脾、症状改善差异无统计学意义(P=0.834，0.232)。携带≥3个突变基因组PMF患者无进展生存期(PFS)明显缩短：734(119~3 301) d vs 1 904(479~5 461) d(H=-2.387，P=0.017)。携带TET2、ASXL1、EZH2或TP53基因突变与未突变组比较经芦可替尼治疗前后的脾脏缩小及症状改善，差异无统计学意义(TET2：P=0.097，0.088；ASXL1：P=0.137，0.692；EZH2：P=0.075，0.655；TP53：P=0.801，0.869)。携带EZH2突变患者PFS明显缩短(P=0.033)，携带TET2、ASXL1、TP53基因突变患者较未携带者PFS未见明显缩短(P=0.071，0.563，0.787)。结论 非驱动突变对芦可替尼的缩脾及体质性症状改善等疗效存在一定影响。Abstract: Objective To explore the effect of non-driver mutations on the treatment of patients with primary myelofibrosis(PMF) with ruxolitinib.Methods The clinical data of 46 patients with PMF who were initially diagnosed in the Hematology Department of Weifang People's Hospital from January 1, 2017 to March 1, 2022 were retrospectively analyzed to explore the relationship between non-driver mutations and the efficacy of ruxolitinib.Results Forty-four of 46 patients with PMF had mutations detected, of which 6 patients had triple-negative driver mutations, and 2 patients had no mutations detected. There were 21 patients with ≥3 gene mutations and 25 patients with < 3 mutations. Ruxolitinib still had a better effect on shrinking spleen and improving physical symptoms in PMF patients with ≥3 mutations(P=0.002, 0.045). There was no significant difference in shrinking spleen and improving symptoms after treatment with Ruxolitinib compared with < 3 mutations group(P=0.834, 0.232). PFS of PMF patients with ≥3 mutations was significantly shortened: 734(119-3 301) d vs 1 904(479-5 461) d(H=-2.387, P=0.017). There was no significant difference in spleen shrinkage and symptom improvement between the group with TET2, ASXL1, EZH2 or TP53 gene mutation and the group without mutation(TET2: P=0.097, 0.088; ASXL1: P=0.137, 0.692; EZH2: P=0.075, 0.655; TP53: P=0.801, 0.869). The PFS of patients with EZH2 mutation was significantly shortened(P=0.033), and the total PFS of patients with TET2, ASXL1, and TP53 gene mutations was not significantly shortened than that of patients without EZH2 mutation(P=0.071, 0.563, 0.787).Conclusion The non-driver mutations have a certain effect on the effect of ruxolitinib on spleen contraction and improvement of physical symptoms.
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Key words:
- ruxolitinib /
- non-driver mutations /
- primary myelofibrosis
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表 1 2组患者的临床数据资料
中位数(范围) 临床特征 ≥3个基因突变(n=21) < 3个基因突变(n=25) 统计值 P 性别(男/女)/例 12/9 13/12 χ2=0.342 0.734 年龄/岁 65(57~78) 57(44~74) H=1.630 0.125 WBC/(×109/L) 21.9(5.4~105.5) 14.1(2.3~30.6) H=0.613 0.550 HGB/(g/L) 104(43~143) 108(82~132) H=-0.258 0.800 PLT/(×109/L) 307(20~1 300) 404(142~819) H=-0.552 0.590 脾脏长径/cm 治疗前 19.9(11.0~30.1) 20.6(11.0~28.0) H=-0.252 0.805 治疗后 16.8(11.0~25.0) 16.4(11.0~22.0) H=0.214 0.834 统计值 Z=4.604 Z=2.961 P 0.002 0.025 MPN-10评分/分 治疗前 23(6~45) 26(0~56) H=-0.355 0.728 治疗后 14(5~25) 9(3~17) H=1.251 0.232 统计值 t=2.377 t=3.087 P 0.045 0.021 LDH/(U/L) 704(265~1 731) 831(136~1 798) H=-0.416 0.684 DIPSS评分/分 2.4(1.0~5.0) 2.3(1.0~5.0) H=0.253 0.804 PFS/d 734(119~3 301) 1 904(479~5 461) H=-2.387 0.017 
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表 2 伴有不同非驱动基因突变对芦可替尼治疗PMF患者的影响
中位数(范围) 突变基因 例数 MPN10评分/分 脾脏长径/cm 治疗前 治疗后 t P 治疗前 治疗后 t P TET2 -1.832 0.088 -1.780 0.097 有 20 20(6~33) 12(5~25) 17.3(11.0~21.2) 16.0(11.0~25.0) 无 26 30(12~56) 12(3~23) 22.2(16.0~30.1) 17.4(11.9~27.2) ASXL1 -0.404 0.692 -1.579 0.137 有 14 24(9~45) 13(3~25) 20.8(16.0~30.1) 19.5(11.9~27.2) 无 32 25(6~56) 12(5~23) 18.0(11.0~28.0) 13.6(11.0~19.1) EZH2 0.456 0.655 -1.922 0.075 有 5 26(6~54) 11(5~23) 21.7(17.6~30.1) 22.1(17.0~27.2) 无 41 24(9~56) 12(3~25) 18.7(11.0~28.0) 14.8(11.0~23.2) TP53 0.169 0.869 0.257 0.801 有 5 21(11~28) 8(5~13) 18.1(11.0~24.2) 14.7(11.0~17.0) 无 41 25(6~56) 13(3~25) 19.7(11.0~30.1) 17.0(11.0~27.2)
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