Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis
Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis
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DOI：
10.1182/blood-2013-02-485888
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发表时间：
2013-12-12
期刊：
影响因子：
20.3
通讯作者：
Gisslinger, Heinz
中科院分区：
文献类型：
--
作者：
Cervantes, Francisco;Vannucchi, Alessandro M.;Gisslinger, Heinz
Ruxolitinib是一种有效的Janus Kinase(JAK)1/JAK2抑制剂，已显示出迅速减少脾肿大并显著改善骨髓纤维化(MF)患者的疾病相关症状和生活质量。目前的分析报告了口服Janus相关激酶(JAK)抑制剂治疗II(Comfort-II试验)的受控骨髓纤维化研究的有效性和安全性的3年随访(中位数，151周)，比较了鲁索利替尼和最佳可用疗法(BAT)在219例中2型和高危MF患者中的疗效和安全性。在Ruxolitinib组，通过继续治疗，通过磁共振成像将脾体积缩小35%(相当于通过触诊缩小约50%)至少持续了144周，在患者中实现这种程度反应的概率为50%(95%可信区间[CI]，36-63)。在这项分析时，45%的随机服用鲁索利替尼的患者仍在接受治疗。鲁索利替尼的耐受性仍然很好。贫血和血小板减少是主要的毒副作用，但它们通常是可控的，随着时间的推移而改善，很少导致停止治疗(分别为1%和3.6%的患者)。在超过1名患者中，没有单一的非血液学不良事件导致鲁索利替尼最终停用。此外，随机服用鲁索利替尼的患者比随机服用BAT的患者显示出更长的总存活率(风险比，0.48；95%可信区间，0.28-0.85；对数等级检验，P=0.009)。这项试验在Clinicaltrials.gov上注册为#NCT00934544。
Ruxolitinib is a potent Janus kinase (JAK)1/JAK2 inhibitor that has demonstrated rapid reductions in splenomegaly and marked improvement in disease-related symptoms and quality of life in patients with myelofibrosis (MF). The present analysis reports the 3-year follow-up (median, 151 weeks) of the efficacy and safety of Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II (the COMFORT-II Trial), comparing ruxolitinib with the best available therapy (BAT) in 219 patients with intermediate-2 and high-risk MF. In the ruxolitinib arm, with continued therapy, spleen volume reductions of >= 35% by magnetic resonance imaging (equivalent to approximately 50% reduction by palpation) were sustained for at least 144 weeks, with the probability of 50% (95% confidence interval [CI], 36-63) among patients achieving such degree of response. At the time of this analysis, 45% of the patients randomized to ruxolitinib remained on treatment. Ruxolitinib continues to be well tolerated. Anemia and thrombocytopenia were the main toxicities, but they were generally manageable, improved over time, and rarely led to treatment discontinuation (1% and 3.6% of patients, respectively). No single nonhematologic adverse event led to definitive ruxolitinib discontinuation in more than 1 patient. Additionally, patients randomized to ruxolitinib showed longer overall survival than those randomized to BAT (hazard ratio, 0.48; 95% CI, 0.28-0.85; log-rank test, P = .009). This trial was registered at clinicaltrials.gov as #NCT00934544.