Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy;
Blood. 2014 Apr 3;123(14):2157-60. doi: 10.1182/blood-2013-11-536557. Epub 2014 Jan 23.
The JAK1/JAK2 inhibitor ruxolitinib produced significant reductions in splenomegaly and symptomatic burden and improved survival in patients with myelofibrosis (MF), irrespective of their JAK2 mutation status, in 2 phase III studies against placebo (COMFORT-I) and best available therapy (COMFORT-II). We performed a comprehensive mutation analysis to evaluate the impact of 14 MF-associated mutations on clinical outcomes in 166 patients included in COMFORT-II. We found that responses in splenomegaly and symptoms, as well as the risk of developing ruxolitinib-associated anemia and thrombocytopenia, occurred at similar frequencies across different mutation profiles. Ruxolitinib improved survival independent of mutation profile and reduced the risk of death in patients harboring a set of prognostically detrimental mutations (ASXL1, EZH2, SRSF2, IDH1/2) with an hazard ratio of 0.57 (95% confidence interval: 0.30-1.08) vs best available therapy. These data indicate that clinical efficacy and survival improvement may occur across different molecular subsets of patients with MF treated with ruxolitinib.
在两项针对安慰剂（COMFORT-I）和最佳可用疗法（COMFORT-II）的 III 期研究中，JAK1/JAK2 抑制剂芦可替尼可显著减少骨髓纤维化（MF）患者的脾肿大和症状负担，并改善生存，无论其 JAK2 突变状态如何。我们进行了全面的突变分析，以评估 166 名 COMFORT-II 患者中 14 种与 MF 相关的突变对临床结局的影响。我们发现，脾肿大和症状的反应，以及发生芦可替尼相关贫血和血小板减少的风险，在不同的突变谱中出现的频率相似。芦可替尼改善了生存，与突变谱无关，并降低了携带一组预后不良突变（ASXL1、EZH2、SRSF2、IDH1/2）的患者的死亡风险，其危险比为 0.57（95%置信区间：0.30-1.08），而不是最佳可用疗法。这些数据表明，芦可替尼治疗的 MF 患者的不同分子亚群可能出现临床疗效和生存改善。
