Venetoclax-obinutuzumab (Ven-Obi) 是针对既往未经治疗的慢性淋巴细胞白血病 (CLL) 患者的标准治疗方法。在 CLL14 研究中，先前未接受治疗的 CLL 和合并症患者被随机接受 12 个周期的 Ven-Obi (n=216) 或苯丁酸氮芥-obinutuzumab (Clb-Obi，n=216)。无进展生存期（PFS）是主要终点。关键的次要终点包括下次治疗时间（TTNT）、不可检测的微小残留病（uMRD）发生率、总生存期（OS）和不良事件发生率。分析了患者报告的生活质量 (QoL) 彻底恶化 (TUDD) 之前的时间结果 (PRO)。中位观察时间为 76.4 个月，Ven-Obi 的 PFS 仍然优于 Clb-Obi（中位 76.2 个月 vs 36.4 个月；HR 0.40[95% CI 0.31-0.52]，p<0.0001）。同样，Ven-Obi 后 TTNT 更长（6 年 TTNT 65.2% vs 37.1%；HR 0.44，95% CI 0.33-0.58，p<0.0001）。在 Ven-Obi 组中，存在 del(17p)、未突变的 IGHV 和淋巴结大小≥5 cm 是较短 PFS 的独立预后因素。治疗五年后，Ven-Obi 组中有 17 名患者（意向治疗人群的 7.9%）出现 uMRD（外周血<10-4），而 Clb-Obi 组有 4 名患者（占意向治疗人群的 7.9%）。 Ven-Obi 组的 6 年 OS 率为 78.7%，Clb-Obi 组为 69.2%（HR 0.69[95%CI 0.48-1.01]，p=0.052）。与 Clb-Obi 组相比，Ven-Obi 组的整体健康状况/QoL TUDD 显着更长（中位时间 82.1 个月 vs 65.1 个月；HR 0.70[95%CI 0.51-0.97]）。 Ven-Obi 组和 Clb-Obi 组的随访调整 SPM 发生率分别为 2.3 和 1.4/1000 患者月。持续的长期生存、uMRD 和 QoL 益处支持在 CLL 中使用一年固定期限的 Ven-Obi。 NCT02242942，EudraCT 2014-001810-24。版权所有 © 2024 美国血液学会。

Venetoclax-obinutuzumab (Ven-Obi) is a standard-of-care for patients with previously untreated chronic lymphocytic leukemia (CLL). In the CLL14 study, patients with previously untreated CLL and coexisting conditions were randomized to 12 cycles of Ven-Obi (n=216) or chlorambucil-obinutuzumab (Clb-Obi, n=216). Progression-free survival (PFS) was the primary endpoint. Key secondary endpoints included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS) and rates of adverse events. Patient reported outcomes (PROs) of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared to Clb-Obi (median 76.2 vs 36.4 months; HR 0.40[95%CI 0.31-0.52], p<0.0001). Likewise, TTNT was longer after Ven-Obi (6-year-TTNT 65.2% vs 37.1%; HR 0.44, 95%CI 0.33-0.58, p<0.0001). In the Ven-Obi arm, presence of del(17p), unmutated-IGHV and lymph node size ≥5 cm were independent prognostic factors for shorter PFS. Five years after treatment, 17 patients (7.9% of intention-to-treat-population) in the Ven-Obi arm had uMRD (<10-4 in peripheral blood) compared to 4 (1.9%) in the Clb-Obi arm. 6-year-OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR 0.69[95%CI 0.48-1.01], p=0.052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi compared to the Clb-Obi arm (median 82.1 vs 65.1 months; HR 0.70[95%CI 0.51-0.97]). Follow-up adjusted SPM incidence rates were 2.3 and 1.4/1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival, uMRD and QoL benefits support the use of one-year fixed-duration Ven-Obi in CLL. NCT02242942, EudraCT 2014-001810-24.Copyright © 2024 American Society of Hematology.