Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib
Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib
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DOI：
10.1182/blood-2014-10-606038
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发表时间：
2015-04-16
期刊：
影响因子：
20.3
通讯作者：
O'Brien, Susan
中科院分区：
文献类型：
--
作者：
Byrd, John C.;Furman, Richard R.;O'Brien, Susan
伊布鲁替尼是一种口服的Bruton酪氨酸激酶抑制剂，可拮抗B细胞受体、趋化因子和整合素介导的信号转导。在早期研究中，伊布鲁替尼在慢性淋巴细胞白血病(CLL)中表现出高应答率和延长无进展生存期(PFS)。使用伊布鲁替尼观察到的持久反应在一定程度上与适度的毒性有关，这允许大多数患者接受较长时间的持续治疗。我们报告了132例有症状治疗的患者的中位3年随访期--初治和复发/难治性CLL或小淋巴细胞性淋巴瘤。随着时间的推移，伊布鲁替尼的治疗时间越长，反应质量越好，持续缓解的时间越长。随着随访时间的延长，3级或更严重的细胞减少、疲乏和感染的发生率降低。进展仍然不常见，主要发生在一些复发的del(17)(p13.1)和/或del(11)(q22.3)病患者。即使持续1年，与治疗相关的淋巴细胞增多症仍基本无症状，与部分缓解或更好的患者相比，似乎不会改变较长期的PFS和总存活率。总而言之，这些数据提供了证据，表明ibrutinib控制了CLL疾病的表现，并在较长时间内具有良好的耐受性；这些信息可以帮助指导不同亚组的潜在治疗选择，以降低复发的长期风险。
Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naive and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse.