Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
St. Vincent's Hospital, Melbourne, VIC, Australia.
Blood. 2022 Jun 2;139(22):3278-3289. doi: 10.1182/blood.2021014488.
CAPTIVATE (NCT02910583) is an international phase 2 study in patients aged ≤70 years with previously untreated chronic lymphocytic leukemia (CLL). Results from the cohort investigating fixed-duration (FD) treatment with ibrutinib plus venetoclax are reported. Patients received 3 cycles of ibrutinib lead-in then 12 cycles of ibrutinib plus venetoclax (oral ibrutinib [420 mg/d]; oral venetoclax [5-week ramp-up to 400 mg/d]). The primary endpoint was complete response (CR) rate. Hypothesis testing was performed for patients without del(17p) with prespecified analyses in all treated patients. Secondary endpoints included undetectable minimal residual disease (uMRD) rates, progression-free survival (PFS), overall survival (OS), and safety. Of the 159 patients enrolled and treated, 136 were without del(17p). The median time on study was 27.9 months, and 92% of patients completed all planned treatment. The primary endpoint was met, with a CR rate of 56% (95% confidence interval [CI], 48-64) in patients without del(17p), significantly higher than the prespecified 37% minimum rate (P < .0001). In the all-treated population, CR rate was 55% (95% CI, 48-63); best uMRD rates were 77% (peripheral blood [PB]) and 60% (bone marrow [BM]); 24-month PFS and OS rates were 95% and 98%, respectively. At baseline, 21% of patients were in the high tumor burden category for tumor lysis syndrome (TLS) risk; after ibrutinib lead-in, only 1% remained in this category. The most common grade ≥3 adverse events (AEs) were neutropenia (33%) and hypertension (6%). First-line ibrutinib plus venetoclax represents the first all-oral, once-daily, chemotherapy-free FD regimen for patients with CLL. FD ibrutinib plus venetoclax achieved deep, durable responses and promising PFS, including in patients with high-risk features.
CAPTIVATE（NCT02910583）是一项在年龄≤70 岁、未经治疗的慢性淋巴细胞白血病（CLL）患者中进行的国际 2 期研究。报告了研究固定疗程（FD）治疗伊布替尼加维奈托克的队列结果。患者接受 3 个周期的伊布替尼导入，然后接受 12 个周期的伊布替尼加维奈托克（口服伊布替尼[420mg/d]；口服维奈托克[5 周剂量爬坡至 400mg/d]）。主要终点是完全缓解（CR）率。对无 del(17p)的患者进行了假设检验，并对所有治疗患者进行了预设分析。次要终点包括不可检测的微小残留病（uMRD）率、无进展生存期（PFS）、总生存期（OS）和安全性。在入组和治疗的 159 名患者中，136 名患者无 del(17p)。研究中位时间为 27.9 个月，92%的患者完成了所有计划治疗。主要终点达到，无 del(17p)患者的 CR 率为 56%（95%CI，48-64），显著高于预设的 37%最小率（P<.0001）。在所有治疗人群中，CR 率为 55%（95%CI，48-63）；最佳 uMRD 率分别为 77%（外周血[PB]）和 60%（骨髓[BM]）；24 个月 PFS 和 OS 率分别为 95%和 98%。基线时，21%的患者有肿瘤溶解综合征（TLS）风险的高肿瘤负担类别；伊布替尼导入后，仅有 1%的患者仍处于该类别。最常见的≥3 级不良事件（AE）是中性粒细胞减少（33%）和高血压（6%）。一线伊布替尼加维奈托克是首个用于 CLL 的全口服、每日一次、无化疗 FD 方案。FD 伊布替尼加维奈托克实现了深度、持久的缓解，具有良好的 PFS，包括在高风险特征的患者中。
