Ruxolitinib versus standard therapy for the treatment of polycythemia vera.
Ruxolitinib versus standard therapy for the treatment of polycythemia vera.
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DOI：
10.1056/nejmoa1409002
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发表时间：
2015-01-29
期刊：
影响因子：
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通讯作者：
Verstovsek S
中科院分区：
文献类型：
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作者：
Vannucchi AM;Kiladjian JJ;Griesshammer M;Masszi T;Durrant S;Passamonti F;Harrison CN;Pane F;Zachee P;Mesa R;He S;Jones MM;Garrett W;Li J;Pirron U;Habr D;Verstovsek S
Ruxolitinib是一种Janus激酶（JAK）1和2抑制剂，在一项2期研究中显示对真性红细胞增多症患者具有临床获益。我们进行了一项3期开放标签研究，以评估鲁索利替尼与标准疗法相比，在对羟基脲反应不充分或出现不可接受的副作用的真性红细胞增多症患者中的疗效和安全性。我们以1：1的比例将静脉切开术依赖性脾肿大患者随机分配接受ruxolitinib（110例患者）或标准治疗（112例患者）。主要终点是第32周的红细胞压积控制和第32周时脾脏体积至少减少35%，通过成像评估。鲁索替尼组有21%的患者达到了主要终点，而标准治疗组只有1%（P<0.001）。60%接受ruxolitinib治疗的患者和20%接受标准治疗的患者实现了红细胞压积控制;两组分别有38%和1%的患者脾脏体积至少减少35%。鲁索利替尼组24%的患者和标准治疗组9%的患者实现了血液学完全缓解（P = 0.003）; 49%对5%的患者在第32周时总症状评分至少降低50%。在ruxolitinib组中，2%的患者发生3级或4级贫血，5%的患者发生3级或4级血小板减少;标准治疗组的相应百分比为0%和4%。鲁索利替尼组6%的患者和标准治疗组0%的患者报告带状疱疹感染（所有病例均为1级或2级）。1例接受ruxolitinib治疗的患者和6例接受标准治疗的患者发生血栓栓塞事件。在对羟基脲反应不足或有不可接受的副作用的患者中，鲁索替尼在控制红细胞压积、减少脾脏体积和改善真性红细胞增多症相关症状方面优于标准治疗上级。
Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P = 0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard- therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy. In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera.