Clinical Trials Office, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY.
Division of Hematology & Hematological Malignancies, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada.
Blood Adv. 2022 Jun 14;6(11):3440-3450. doi: 10.1182/bloodadvances.2021006434.
We report long-term follow-up from the RESONATE-2 phase 3 study of the once-daily Bruton's tyrosine kinase inhibitor ibrutinib, which is the only targeted therapy with significant progression-free survival (PFS) and overall survival (OS) benefit in multiple randomized chronic lymphocytic leukemia (CLL) studies. Patients (≥65 years) with previously untreated CLL, without del(17p), were randomly assigned 1:1 to once-daily ibrutinib 420 mg until disease progression/unacceptable toxicity (n = 136) or chlorambucil 0.5-0.8 mg/kg ≤12 cycles (n = 133). With up to 8 years of follow-up (range, 0.1-96.6 months; median, 82.7 months), significant PFS benefit was sustained for ibrutinib vs chlorambucil (hazard ratio [HR], 0.154; 95% confidence interval [CI], 0.108-0.220). At 7 years, PFS was 59% for ibrutinib vs 9% for chlorambucil. PFS benefit was also observed for ibrutinib- vs chlorambucil-randomized patients with high-risk genomic features: del(11q) (HR, 0.033; 95% CI, 0.010-0.107) or unmutated immunoglobulin heavy chain variable region (HR, 0.112; 95% CI, 0.065-0.192). OS at 7 years was 78% with ibrutinib. Prevalence of adverse events (AEs) was consistent with previous 5-year follow-up. Ibrutinib dosing was held (≥7 days) for 79 patients and reduced for 31 patients because of AEs; these AEs resolved or improved in 85% (67 of 79) and 90% (28 of 31) of patients, respectively. With up to 8 years of follow-up, 42% of patients remain on ibrutinib. Long-term RESONATE-2 data demonstrate sustained benefit with first-line ibrutinib treatment for CLL, including for patients with high-risk genomic features. These trials were registered at www.clinicaltrials.gov as #NCT01722487 and #NCT01724346.
我们报告了每日一次布鲁顿酪氨酸激酶抑制剂伊布替尼的 RESONATE-2 期 3 研究的长期随访结果，该药物是唯一在多项随机慢性淋巴细胞白血病（CLL）研究中具有显著无进展生存期（PFS）和总生存期（OS）获益的靶向治疗药物。患有未经治疗的 CLL（年龄≥65 岁）、无 del(17p)的患者按 1:1 随机分配，每日一次接受伊布替尼 420mg 治疗，直至疾病进展/无法耐受毒性（n=136）或接受氯苯丁酸氮芥 0.5-0.8mg/kg≤12 个周期（n=133）。随访时间最长达 8 年（范围，0.1-96.6 个月；中位数，82.7 个月），与氯苯丁酸氮芥相比，伊布替尼持续显著延长了 PFS（风险比[HR]，0.154；95%置信区间[CI]，0.108-0.220）。7 年时，伊布替尼组的 PFS 为 59%，而氯苯丁酸氮芥组为 9%。伊布替尼与氯苯丁酸氮芥随机分组的高危基因组特征患者也观察到 PFS 获益：del(11q)（HR，0.033；95%CI，0.010-0.107）或未突变免疫球蛋白重链可变区（HR，0.112；95%CI，0.065-0.192）。7 年时伊布替尼组的 OS 为 78%。不良事件（AE）的发生率与之前的 5 年随访结果一致。79 例患者因 AE 停药（≥7 天），31 例患者减少剂量；这些 AE 分别有 85%（67/79）和 90%（28/31）的患者得到解决或改善。在最长 8 年的随访中，42%的患者仍在接受伊布替尼治疗。RESONATE-2 的长期数据显示，伊布替尼作为 CLL 的一线治疗具有持续获益，包括对具有高危基因组特征的患者。这些试验在 www.clinicaltrials.gov 上注册为#NCT01722487 和#NCT01724346。
