Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab
Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab
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DOI：
10.1182/blood-2018-08-870238
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发表时间：
2019-05-09
期刊：
影响因子：
20.3
通讯作者：
Brown, Jennifer R.
中科院分区：
文献类型：
--
作者：
Byrd, John C.;Hillmen, Peter;Brown, Jennifer R.
每日一次口服布鲁顿酪氨酸激酶抑制剂伊曲替尼可显著改善慢性淋巴细胞白血病（CLL）患者的预后。III期RESONATE试验比较了单药伊鲁替尼与奥法木单抗在高风险、复发性CLL患者中的疗效，为伊鲁替尼在美国和欧洲的批准提供了支持。我们描述了接受RESONATE治疗的患者的长期随访，观察到无进展生存期（PFS）的持续优效性（风险比[HR]，0.133; 95%置信区间[CI]，0.099-0.178）。总生存期获益持续（HR，0.591; 95% CI，0.378-0.926），尽管与奥法木单抗治疗患者交叉至伊鲁替尼之前观察到的获益相比，获益幅度有所降低（HR，0.426; 95% CI，0.220-0.823）。值得注意的是，对伊鲁替尼的总体反应随着时间的推移而增加，91%的患者获得反应。伊曲替尼的PFS获益与基线风险因素无关，尽管既往接受过≥ 2次治疗的患者的PFS通常比发生≥ 3次不良事件的患者短，但随着时间的推移，PFS通常会降低，仅导致一小部分患者停止治疗。27%的患者因疾病进展而停用伊鲁替尼。这项长期研究为伊克替尼在复发性/难治性CLL中的持续疗效和安全性提供了支持，并考虑了在明确证明获益时允许交叉至试验性治疗的研究规定。
Ibrutinib, a once-daily oral inhibitor of Bruton tyrosine kinase, has greatly improved outcomes for patients with chronic lymphocytic leukemia (CLL). The phase 3 RESONATE trial, which compared single-agent ibrutinib to ofatumumab in high-risk, relapsed patients with CLL, provided support for approval of ibrutinib in the United States and Europe. We describe long-term follow-up of patients treated in RESONATE, where continued superiority of progression-free survival (PFS) (hazard ratio [HR], 0.133; 95% confidence interval [CI], 0.099-0.178) was observed. Overall survival benefit continues (HR, 0.591; 95% CI, 0.378-0.926), although with decreased magnitude relative to that seen before crossover to ibrutinib was implemented for patients on ofatumumab (HR, 0.426; 95% CI, 0.220-0.823). Notably, overall response to ibrutinib increased over time, with 91% of patients attaining a response. The PFS benefit with ibrutinib was independent of baseline risk factors, although patients with >= 2 prior therapies had shorter PFS than those with = 3 adverse events generally decreased over time, causing only a small proportion of patients to cease therapy. Ibrutinib was discontinued due to progressive disease in 27% of patients. This long-term study provides support for sustained efficacy and safety of ibrutinib in relapsed/refractory CLL and consideration of study provisions that allow crossover to investigational therapy when benefit has been clearly demonstrated.