芦可替尼治疗真性红细胞增多症的疗效及安全性评价

Efficacy and Safety of Ruxolitinib in Polycythemia Vera

目的:评价芦可替尼治疗真性红细胞增多症(PV)的疗效及安全性。方法:回顾性分析2013年1月至2019年12月北京协和医院接受芦可替尼治疗的PV患者的临床资料。芦可替尼起始剂量均为10 mg bid,治疗满3个月后,如果红细胞压积(HCT)控制不良,可以增加芦可替尼剂量。无需额外放血且HCT<45%被视为HCT缓解。结果:共33例接受了芦可替尼治疗的PV患者纳入研究,男性17例,女性16例,中位年龄50(21-72)岁。JAK2V617F突变31例,JAK2 exon12突变2例。接受治疗前中位血红蛋白187(166-208)g/L,白细胞10.4(5.0-15.8)×10^(9)/L,血小板457(237-677)×10^(9)/L。17例(51.5%)患者因羟基脲耐药或不耐受接受芦可替尼二线治疗,16例(48.5%)自愿接受一线芦可替尼治疗。中位起病至接受芦可替尼治疗时间47(3-188)月。随访至2019年12月31日,所有患者均坚持用药,接受芦可替尼治疗中位时间19(2-91)个月。一线与二线治疗者中均有15例(分别占93.8%和88.2%)获得HCT缓解。中位开始治疗至HCT缓解的时间是2.2(0.8-11.6)个月,截止目前获得HCT缓解后疗效丧失者1例(3.0%)。最常见的血液学不良事件包括贫血和血小板计数降低,根据CTCAE不良反应分级,其中1级贫血1例(3.0%),2级血小板减少1例(3.0%)。芦可替尼治疗期间均未出现新发血栓事件者。结论:芦可替尼治疗PV患者HCT缓解率高,不良反应少见,患者可以长期坚持用药。

Objective: To evaluate the efficacy and safety of ruxolitinib in patients with polycythemia vera(PV).Methods: The clinical data of patients with PV treated with ruxolitinib in Peking Union Medical College Hospital from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The starting dose of oral ruxolitinib was 10 mg twice daily and could be increased after 3 months of treatment if hematocrit(HCT) control was not achieved. HCT control was defined as HCT<45% in the absence of phlebotomy. Results: Thirty-three patients(17 males and 16 females) were treated with ruxolitinib at a median age of 50(21-72) years. JAK2V617F and JAK2exon12 alleles were detected in 31 and 2 patients, respectively. Before treatment, median hemoglobin level was 187(166-208) g/L, median white blood cell and platelet level was 10.4(5.0-15.8)×10^(9)/L and 457(237-677)×10^(9)/L, respectively. Totally 17 patients(51.5%) who were resistant to or intolerant of hydroxyurea were treated with ruxolitinib as second-line therapy, and 16 patients(48.5%) were treated with ruxolitinib as first-line therapy voluntarily. The median time since PV diagnosis to treatment of ruxolitinib was 47(3-188) months. By December 31, 2019, all the patients continued to receive ruxolitinib. The median duration of ruxolitinib exposure was 19(2-91) months. Both in the first-line therapy group and second-line therapy group, 15 cases(accounting for 93.8% and 88.2%, respecitvely) achieved HCT control. The median time from start of therapy to HCT control was 2.2(0.8-11.6) months. One patient(3.0%) had disease progression after HCT control. The most common hematologic adverse events included anemia and thrombocytopenia, according to CTCAE classification, including 1 case of grade 1 anemia(3.0%) and 1 case of grade 2 thrombocytopenia(3.0%). There was no thromboembolic event occurred during the therapy of ruxolitinib. Conclusion: The remission rate of HCT in PV patients treated with ruxolitinib is high,and adverse reactions are rare. Ruxolitinib is effective in HCT control and generally well tolerated in patients with PV.