Mead Adam J, Milojkovic Dragana, Knapper Steven, Garg Mamta, Chacko Joseph, Farquharson Mira, Yin John, Ali Sahra, Clark Richard E, Andrews Chris, Dawson Meryem Ktiouet, Harrison Claire
MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK.
Br J Haematol. 2015 Jul;170(1):29-39. doi: 10.1111/bjh.13379. Epub 2015 Mar 30.
Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The primary composite endpoint was the proportion of patients achieving treatment success [≥ 50% reduction in palpable spleen length and/or a ≥ 50% decrease in Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF TSS)] at 48 weeks. This was the first time that efficacy of ruxolitinib in myelofibrosis has been evaluated based on these criteria and the first time the MF-SAF was used in a population of patients solely from the United Kingdom. Overall, 50% of patients and 57% of intermediate-1 risk patients, achieved treatment success; reductions in spleen length and symptoms were observed in all risk groups. The majority of patients (66.7%) experienced ≥ 50% reductions from baseline in spleen length at any time. Improvements in MF-SAF TSS were seen in 80.0%, 72.7%, and 72.2% of intermediate-1, intermediate-2, and high-risk patients, respectively. Consistent with other studies of ruxolitinib, the most common haematological adverse events were anaemia and thrombocytopenia. Results indicate that most patients with myelofibrosis, including intermediate-1 risk patients, may benefit from ruxolitinib treatment.
骨髓纤维化的特征是脾肿大和使人虚弱的全身症状，这些症状会对患者的生活质量产生负面影响。ROBUST是一项在英国开展的开放标签II期研究，评估了鲁索替尼对骨髓纤维化患者（N = 48）的安全性和疗效，其中包括中危-1级患者。主要复合终点是在48周时达到治疗成功的患者比例[可触及脾脏长度减少≥50%和/或骨髓纤维化症状评估表总症状评分（MF-SAF TSS）降低≥50%]。这是首次基于这些标准评估鲁索替尼在骨髓纤维化中的疗效，也是首次在仅来自英国的患者群体中使用MF-SAF。总体而言，50%的患者和57%的中危-1级患者达到了治疗成功；在所有风险组中均观察到脾脏长度和症状的减轻。大多数患者（66.7%）在任何时候脾脏长度较基线均减少≥50%。中危-1级、中危-2级和高危患者中分别有80.0%、72.7%和72.2%的患者MF-SAF TSS有所改善。与其他鲁索替尼研究一致，最常见的血液学不良事件是贫血和血小板减少。结果表明，大多数骨髓纤维化患者，包括中危-1级患者，可能从鲁索替尼治疗中获益。
