Kirito Keita, Suzuki Kenshi, Miyamura Koichi, Takeuchi Masahiro, Handa Hiroshi, Okamoto Shinichiro, Gadbaw Brian, Yamauchi Kyosuke, Amagasaki Taro, Ito Kazuo, Hino Masayuki
Department of Hematology and Oncology, University of Yamanashi, 1110 Simokawakita, Chuou-shi, Yamanashi, 409-3898, Japan.
Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan.
Int J Hematol. 2018 Feb;107(2):173-184. doi: 10.1007/s12185-017-2333-y. Epub 2017 Sep 27.
Ruxolitinib, a potent JAK1/JAK2 inhibitor, was found to be superior to the best available therapy (BAT) in controlling hematocrit, reducing splenomegaly, and improving symptoms in the phase 3 RESPONSE study of patients with polycythemia vera with splenomegaly who experienced an inadequate response to or adverse effects from hydroxyurea. We report findings from a subgroup analysis of Japanese patients in RESPONSE (n = 18). The composite response rate (hematocrit control and spleen response) was higher in patients receiving ruxolitinib (50.0%) than in those receiving BAT (8.3%). A total of 50.0% of patients randomized to ruxolitinib achieved a spleen response vs 8.3% of those receiving BAT; 100 and 33.3% of patients in the respective groups achieved hematocrit control, with mean hematocrit in ruxolitinib-treated patients remaining stable at < 45% throughout the study. Similarly, a higher proportion of ruxolitinib-treated patients achieved complete hematologic remission (33.3 vs 16.7%). Ruxolitinib also led to rapid improvements in pruritus. All responses with ruxolitinib were durable to week 80, and its safety profile was consistent with that in the overall study. These findings suggest that ruxolitinib is an effective and well-tolerated treatment option for Japanese patients with polycythemia vera with an inadequate response to or adverse effects from hydroxyurea.
鲁索替尼是一种强效的JAK1/JAK2抑制剂，在一项针对伴有脾肿大且对羟基脲反应不足或出现不良反应的真性红细胞增多症患者的3期RESPONSE研究中，发现其在控制血细胞比容、减轻脾肿大和改善症状方面优于最佳可用疗法（BAT）。我们报告了RESPONSE研究中日本患者亚组分析的结果（n = 18）。接受鲁索替尼治疗的患者的复合缓解率（血细胞比容控制和脾脏反应）高于接受BAT治疗的患者（分别为50.0%和8.3%）。随机接受鲁索替尼治疗的患者中有50.0%实现了脾脏反应，而接受BAT治疗的患者为8.3%；各组中分别有100%和33.3%的患者实现了血细胞比容控制，在整个研究过程中，接受鲁索替尼治疗的患者的平均血细胞比容保持稳定在<45%。同样，接受鲁索替尼治疗的患者中有更高比例实现了完全血液学缓解（33.3%对16.7%）。鲁索替尼还使瘙痒症状迅速改善。鲁索替尼的所有反应在第80周时仍然持久，其安全性与整个研究一致。这些发现表明，鲁索替尼对于对羟基脲反应不足或出现不良反应的日本真性红细胞增多症患者是一种有效且耐受性良好的治疗选择。
