Pirtobrutinib Versus Ibrutinib in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

We report results, to our knowledge, from the first randomized head-to-head comparison of pirtobrutinib versus ibrutinib in BTKi-naïve CLL/SLL in both treatment-naïve (TN) patients and patients with relapsed/refractory (R/R) disease.

据我们所知，我们报告了首次将pirtobrutinib与ibrutinib进行随机头对头比较的结果，这是在既往未接受BTKi治疗的慢性淋巴细胞性白血病/小淋巴细胞性淋巴瘤（CLL/SLL）患者中进行的，包括治疗未接受（TN）患者和复发/难治性（R/R）疾病患者。

patients_and_methods

Patients (N = 662) were randomly assigned 1:1 to receive pirtobrutinib or ibrutinib.

患者（N = 662）被随机1:1分配接受pirtobrutinib或ibrutinib治疗。

All patients were BTKi-naïve.

所有患者均为BTKi初治。

Primary end points were overall response rate (ORR) by independent review committee (IRC) among all randomly assigned patients (intention to treat [ITT]) and in patients with R/R disease.

主要终点是独立审查委员会（IRC）在所有随机分配的患者（意向治疗人群[ITT]）以及复发/难治性疾病患者中评估的总体反应率（ORR）。

Results

The study met its primary end points, demonstrating statistically significant noninferiority (NI) of IRC-ORR for pirtobrutinib versus ibrutinib in both the ITT (87.0% [95% CI, 82.9 to 90.4] v 78.5% [95% CI, 73.7 to 82.9]; ORR ratio = 1.11 [95% CI, 1.03 to 1.19]; two-sided P < .0001) and R/R populations (n = 437; 84.0% [95% CI, 78.5 to 88.6] v 74.8% [95% CI, 68.5 to 80.4]; ORR ratio = 1.12 [95% CI, 1.02 to 1.24]; two-sided P < .0001).

该研究达到了其主要终点，展示了pirtobrutinib与伊布替尼相比在IRC-ORR上具有统计学上显著的非劣效性（NI），在ITT人群中（87.0% [95% CI, 82.9至90.4]对比78.5% [95% CI, 73.7至82.9]；ORR比率=1.11 [95% CI, 1.03至1.19]；双侧P<.0001）以及R/R人群中（n=437；84.0% [95% CI, 78.5至88.6]对比74.8% [95% CI, 68.5至80.4]；ORR比率=1.12 [95% CI, 1.02至1.24]；双侧P<.0001）。

In TN patients (n = 225), IRC-ORR was 92.9% (95% CI, 86.4 to 96.9) with pirtobrutinib versus 85.8% (95% CI, 78.0 to 91.7) with ibrutinib.

在TN患者(n = 225)中，IRC评估的客观缓解率(IRC-ORR)为92.9%(95%置信区间，86.4至96.9)，使用pirtobrutinib治疗，而使用ibrutinib治疗的患者为85.8%(95%置信区间，78.0至91.7)。

Investigator assessed ORR results were consistent.

研究者评估的ORR结果是一致的。

Investigator-assessed progression-free survival(PFS) favored pirtobrutinib in the ITT (hazard ratio[HR], 0.57 [95% CI, 0.39 to 0.83]), R/R (HR, 0.73 [95% CI, 0.47 to 1.13]), and TN (HR, 0.24 [95% CI, 0.10 to 0.59]) populations.

研究者评估的无进展生存期（PFS）在ITT（风险比[HR]，0.57 [95% 置信区间，0.39至0.83]）、R/R（HR，0.73 [95% 置信区间，0.47至1.13]）和TN（HR，0.24 [95% 置信区间，0.10至0.59]）人群中均倾向于pirtobrutinib。

Cardiac adverse eventrates of atrial fibrillation/flutter and hypertension were lower with pirtobrutinib.

与pirtobrutinib相关的房颤/扑动和高血压的心脏不良事件发生率较低。

Conclusions

Pirtobrutinib demonstrated NI of ORR versus ibrutinib, with a favorable early PFS trend, particularly in TN patients, and a favorable safety profile including low rates of atrial fibrillation and hypertension.

Pirtobrutinib显示出与伊布替尼相比的ORR非劣性，早期PFS趋势良好，特别是在TN患者中，且安全性良好，包括房颤和高血压的低发生率。