Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia
Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia
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DOI：
10.1200/jco.19.00895
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发表时间：
2020-04-01
影响因子：
45.3
通讯作者：
Tyner, Jeffrey W.
中科院分区：
文献类型：
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作者：
Dao, Kim-Hien T.;Gotlib, Jason;Tyner, Jeffrey W.
CSF 3R-T618 I是慢性嗜中性粒细胞白血病（CNL）中的一种复发性激活突变，在非典型慢性髓细胞白血病（aCML）中也有较小程度的激活突变，导致组成性JAK-STAT信号传导。我们试图评估JAK 1/2抑制剂ruxolitinib在CNL和aCML患者中的安全性和有效性，无论CSF 3R突变status. METHODS我们进行了一项II期研究ruxolitinib在44例患者（21 CNL和23 aCML）。主要终点是前25例患者在6个连续28天周期结束时的总体血液学缓解率（ORR）。我们将缓解视为部分缓解（PR）或完全缓解（CR）。我们将招募范围扩大到44名患者，以提高我们评估次要终点的能力，包括>= 3级不良事件、脾脏体积、症状评估、反应的遗传相关性和2年生存率。前25名招募患者的结果SORR为32%（8例PR [7例CNL和1例aCML]）。在44例患者的较大队列中，35%有缓解（11例PR [9例CNL和2例aCML]和4例CR [CNL]），50%有致癌CSF 3R突变。与PR组和无应答组相比，CR组6个周期后CSF 3R-T618 I的平均绝对等位基因负荷降低最大。最常见的死亡原因是疾病进展。在34%和14%的患者中分别观察到≥ 3级贫血和血小板减少。没有严重的不良事件归因于ruxolitinib observed.CONCLUSIONRuxolitinib是耐受性良好，并表现出估计的反应率为32%。诊断为CNL和/或携带CSF 3R-T618 I的患者最有可能应答。(c)2019年美国临床肿瘤学会
PURPOSEColony-stimulating factor-3 receptor (CSF3R)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of CSF3R mutation status.METHODSWe conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade >= 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival.RESULTSORR was 32% for the first 25 enrolled patients (8 PR [7 CNL and 1 aCML]). In the larger cohort of 44 patients, 35% had a response (11 PR [9 CNL and 2 aCML] and 4 CR [CNL]), and 50% had oncogenic CSF3R mutations. The mean absolute allele burden reduction of CSF3R-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade >= 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed.CONCLUSIONRuxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most likely to respond. (c) 2019 by American Society of Clinical Oncology