Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial
Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial
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DOI：
10.3324/haematol.2016.143677
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发表时间：
2016-09-01
期刊：
影响因子：
10.1
通讯作者：
Vannucchi, Alessandro M.
中科院分区：
文献类型：
--
作者：
Al-Ali, Haifa Kathrin;Griesshammer, Martin;Vannucchi, Alessandro M.
JUMP是一项针对在临床研究之外无法获得ruxolitinib的患者的3b期扩展访问试验;它是迄今为止在接受ruxolitinib治疗的骨髓纤维化患者中进行的最大规模的临床试验。在这里，我们介绍了对1144例中危或高危骨髓纤维化患者进行分析的安全性和疗效结果，以及对163例中危骨髓纤维化患者进行的单独分析-这些患者未纳入III期COMFORT研究。与ruxolitinib的作用机制一致，最常见的血液学不良事件是贫血和血小板减少，但仅在少数病例中导致治疗中止。最常见的非血液学不良事件主要为1/2级，包括腹泻、发热、疲劳和虚弱。感染率较低，主要为1/2级，未观察到新发或非预期感染。大多数患者的可触及脾脏长度较基线减少>= 50%。根据各种生活质量问卷的评估，症状改善很快，大约一半的患者出现了临床显着改善。中等1风险患者的安全性和疗效特征与总体JUMP人群以及先前报告的中等2风险和高风险患者的安全性和疗效特征一致。总体而言，ruxolitinib在骨髓纤维化患者（包括中度1风险疾病患者）中提供了具有临床意义的脾脏长度和症状减少，其安全性和疗效特征与III期COMFORT研究中观察到的一致。该试验在ClinicalTrials.gov注册为NCT 01493414。
JUMP is a phase 3b expanded-access trial for patients without access to ruxolitinib outside of a clinical study; it is the largest clinical trial to date in patients with myelofibrosis who have been treated with ruxolitinib. Here, we present safety and efficacy findings from an analysis of 1144 patients with intermediate-or high-risk myelofibrosis, as well as a separate analysis of 163 patients with intermediate-1-risk myelofibrosis - a population of patients not included in the phase 3 COMFORT studies. Consistent with ruxolitinib's mechanism of action, the most common hematologic adverse events were anemia and thrombocytopenia, but these led to treatment discontinuation in only a few cases. The most common non-hematologic adverse events were primarily grade 1/2 and included diarrhea, pyrexia, fatigue, and asthenia. The rates of infections were low and primarily grade 1/2, and no new or unexpected infections were observed. The majority of patients achieved a >= 50% reduction from baseline in palpable spleen length. Improvements in symptoms were rapid, with approximately half of all patients experiencing clinically significant improvements, as assessed by various quality-of-life questionnaires. The safety and efficacy profile in intermediate-1-risk patients was consistent with that in the overall JUMP population and with that previously reported in intermediate-2- and high-risk patients. Overall, ruxolitinib provided clinically meaningful reductions in spleen length and symptoms in patients with myelofibrosis, including those with intermediate-1-risk disease, with a safety and efficacy profile consistent with that observed in the phase 3 COMFORT studies. This trial was registered as NCT01493414 at ClinicalTrials.gov.