Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.
Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.
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伊布替尼与奥法木单抗在既往治疗过的慢性淋巴细胞白血病中的比较。
DOI：
10.1056/nejmoa1400376
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发表时间：
2014-07-17
期刊：
影响因子：
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通讯作者：
RESONATE Investigators
中科院分区：
文献类型：
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作者：
Byrd JC;Brown JR;O'Brien S;Barrientos JC;Kay NE;Reddy NM;Coutre S;Tam CS;Mulligan SP;Jaeger U;Devereux S;Barr PM;Furman RR;Kipps TJ;Cymbalista F;Pocock C;Thornton P;Caligaris-Cappio F;Robak T;Delgado J;Schuster SJ;Montillo M;Schuh A;de Vos S;Gill D;Bloor A;Dearden C;Moreno C;Jones JJ;Chu AD;Fardis M;McGreivy J;Clow F;James DF;Hillmen P;RESONATE Investigators
在慢性淋巴细胞白血病（CLL）或小淋巴细胞淋巴瘤（SLL）患者中，治疗反应持续时间短或不良细胞遗传学异常与不良结局相关。我们评估了布鲁顿酪氨酸激酶的共价抑制剂伊曲替尼在有不良结局风险的患者中的疗效。在这项多中心、开放标签、III期研究中，我们将391例复发性或难治性CLL或SLL患者随机分配至每日接受伊鲁替尼或抗CD 20抗体奥法木单抗。主要终点为无进展生存期，次要终点为总生存期和总缓解率。在中位随访9.4个月时，伊鲁替尼显著改善了无进展生存期;伊鲁替尼组未达到中位持续时间（6个月时无进展生存率为88%），而奥法木单抗组的中位持续时间为8.1个月（伊鲁替尼组进展或死亡的风险比为0.22; P<0.001）。伊布替尼还显著改善了总生存率（死亡风险比，0.43; P = 0.005）。在12个月时，伊鲁替尼组的总生存率为90%，奥法木单抗组为81%。伊布替尼组的总体缓解率明显高于奥法木单抗组（42.6%比4.1%，P<0.001）。另外20%的伊替尼治疗患者出现淋巴细胞增多的部分缓解。无论患者是否有染色体17p13.1缺失或对嘌呤类似物耐药，都观察到类似的效果。最常见的非血液学不良事件为伊曲替尼组的腹泻、疲乏、发热和恶心，奥法木单抗组的疲乏、输注相关反应和咳嗽。与奥法木单抗相比，伊曲替尼显著改善了既往接受过治疗的CLL或SLL患者的无进展生存期、总生存期和缓解率。（由Pharmacyclics和Janssen资助; RESONATE ClinicalTrials.gov编号，NCT 01578707。）
In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton’s tyrosine kinase, in patients at risk for a poor outcome. In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.)