Hematology Branch and.
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Blood. 2018 May 24;131(21):2357-2366. doi: 10.1182/blood-2017-12-820910. Epub 2018 Feb 26.
The safety and efficacy of ibrutinib (420 mg) in chronic lymphocytic leukemia (CLL) were evaluated in a phase 2 study; 51 patients had aberration (TP53 cohort) and 35 were enrolled because of age 65 years or older (elderly cohort). Both cohorts included patients with treatment-naive (TN) and relapsed/refractory (RR) CLL. With the median follow-up of 4.8 years, 49 (57.0%) of 86 patients remain on study. Treatment was discontinued for progressive disease in 20 (23.3%) patients and for adverse events in 5 (5.8%). Atrial fibrillation occurred in 18 (20.9%) patients for a rate of 6.4 per 100 patient-years. No serious bleeding occurred. The overall response rate at 6 months, the primary study endpoint, was 95.8% for the TP53 cohort (95% confidence interval, 85.7%-99.5%) and 93.9% for the elderly cohort (95% confidence interval, 79.8%-99.3%). Depth of response improved with time: at best response, 14 (29.2%) of 48 patients in the TP53 cohort and 9 (27.3%) of 33 in the elderly cohort achieved a complete response. Median minimal residual disease (MRD) in peripheral blood was 3.8 × 10 at 4 years, with MRD-negative (<10) remissions in 5 (10.2%) patients. In the TP53 cohort, the estimated 5-year progression-free survival (PFS) was 74.4% in TN-CLL compared with 19.4% in RR-CLL ( = .0002), and overall survival (OS) was 85.3% vs 53.7%, respectively ( = .023). In the elderly cohort, the estimated 5-year PFS and OS in RR-CLL were 64.8% and 71.6%, respectively, and no event occurred in TN-CLL. Long-term administration of ibrutinib was well tolerated and provided durable disease control for most patients. This trial was registered at www.clinicaltrials.gov as #NCT01500733.
在一项 2 期研究中评估了伊布替尼（420mg）在慢性淋巴细胞白血病（CLL）中的安全性和疗效；51 例患者存在异常（TP53 队列），35 例因年龄 65 岁或以上（老年队列）入组。两个队列均包括初治（TN）和复发/难治（RR）CLL 患者。中位随访 4.8 年后，86 例患者中有 49 例（57.0%）仍在研究中。由于疾病进展，20 例（23.3%）患者停止治疗，5 例（5.8%）患者因不良事件停止治疗。18 例（20.9%）患者发生心房颤动，发生率为每 100 患者年 6.4 例。无严重出血事件发生。主要研究终点 6 个月时的总缓解率，TP53 队列为 95.8%（95%置信区间，85.7%-99.5%），老年队列为 93.9%（95%置信区间，79.8%-99.3%）。随着时间的推移，反应深度有所改善：在最佳反应时，TP53 队列中 48 例患者中的 14 例（29.2%）和老年队列中 33 例患者中的 9 例（27.3%）达到完全缓解。4 年时外周血最小残留疾病（MRD）中位数为 3.8×10，5 例（10.2%）患者达到 MRD 阴性（<10）缓解。在 TP53 队列中，TN-CLL 的 5 年无进展生存率（PFS）估计为 74.4%，而 RR-CLL 为 19.4%（P=0.0002），总生存率（OS）分别为 85.3%和 53.7%（P=0.023）。在老年队列中，RR-CLL 的 5 年 PFS 和 OS 估计分别为 64.8%和 71.6%，而 TN-CLL 无事件发生。长期使用伊布替尼耐受性良好，为大多数患者提供了持久的疾病控制。该试验在 www.clinicaltrials.gov 上注册为#NCT01500733。
