Fixed-Duration versus Continuous Treatment for Chronic Lymphocytic Leukemia.

Comparisons of these two therapeutic approaches are lacking.

这两种治疗方法的比较尚缺乏。

Methods

We conducted an investigator-initiated, phase 3, randomized trial involving patients with previously untreated CLL.

我们开展了一项由研究者发起的、针对先前未接受治疗的慢性淋巴细胞白血病（CLL）患者的III期随机试验。

Patients were randomly assigned to receive continuous ibrutinib or fixed-duration venetoclax-obinutuzumab or venetoclax-ibrutinib.

患者被随机分配接受连续的伊布替尼治疗，或固定期限的维奈克拉-奥布替组单抗或维奈克拉-伊布替尼治疗。

The primary end point was investigator-assessed progression-free survival(noninferiority margin for the hazard ratio, 1.608, corresponding to a noninferiority margin of 8 percentage points at 3 years).

主要终点是研究者评估的无进展生存期（风险比的非劣效性边界为1.608，相当于3年时8个百分点的非劣效性边界）。

Secondary end points included minimal residual disease (MRD), response, overall survival, and safety.

次要终点包括微小残留病（MRD）、反应、总生存和安全性。

Results

A total of 909 patients were assigned to venetoclax-obinutuzumab (303 patients), venetoclax-ibrutinib (305 patients), or ibrutinib (301 patients).

共有909名患者被分配到Venetoclax-obinutuzumab组（303名患者）、Venetoclax-ibrutinib组（305名患者）或Ibrutinib组（301名患者）。

The median follow-up was 34.2 months.

中位随访时间为34.2个月。

In this prespecified interim analysis, 3-year progression-free survivalwas 81.1% in the venetoclax-obinutuzumab group, 79.4% in the venetoclax-ibrutinib group, and 81.0% in the ibrutinib group (hazard ratiofor venetoclax-obinutuzumab vs. ibrutinib, 0.87 [98.3% confidence interval{CI}, 0.54 to 1.41]; hazard ratiofor venetoclax-ibrutinib vs. ibrutinib, 0.84 [98.0% CI, 0.53 to 1.32]); the results for each comparison met the criterion for noninferiority.

在这项预先设定的中期分析中，维奈克拉单抗-奥布妥珠单抗组的3年无进展生存率为81.1%，维奈克拉单抗-伊布替尼组为79.4%，伊布替尼组为81.0%（维奈克拉单抗-奥布妥珠单抗与伊布替尼相比，风险比为0.87 [98.3%置信区间（CI），0.54至1.41]；维奈克拉单抗-伊布替尼与伊布替尼相比，风险比为0.84 [98.0% CI，0.53至1.32]）；每项比较的结果均满足非劣效性标准。

After the end of treatment, MRD in peripheral blood was undetectable in 73.3% of the patients in the venetoclax-obinutuzumab group, 47.2% in the venetoclax-ibrutinib group, and 0% in the ibrutinib group.

治疗结束后，维奈克拉单抗-奥布妥珠单抗组中有73.3%的患者的外周血中未检测到微小残留病灶（MRD），维奈克拉单抗-伊布替尼组为47.2%，而伊布替尼组为0%。

Three-year overall survivalwas 91.5%, 96.0%, and 95.7%, respectively.

三年总生存率分别为91.5%、96.0%和95.7%。

The most common adverse events were infections, gastrointestinal disorders, and cytopenias.

最常见的不良事件是感染、胃肠道疾病和细胞减少症。

Conclusions

In patients with previously untreated CLL, fixed-duration treatment with venetoclax-obinutuzumab or venetoclax-ibrutinib was noninferior to continuous ibrutinib with regard to investigator-assessed progression-free survival. (Funded by the University of Cologne and others; CLL17 ClinicalTrials.gov number, NCT04608318; EudraCT number, 2019-003854-99.).

在先前未经治疗的慢性淋巴细胞白血病（CLL）患者中，维奈克拉珠单抗或维奈克拉伊布替尼的固定期限治疗在研究者评估的无进展生存（PFS）方面与持续伊布替尼治疗相比显示出非劣效性。