BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Methods

Patients with previously untreated CLL/SLL without del(17p) were randomly assigned 1:1 to continuous pirtobrutinib monotherapy or BendaR, stratified by immunoglobulin heavy chain gene mutation status and Rai stage.

未接受过治疗的 CLL/SLL 患者，且不伴有 del(17p) 的患者被随机分配为 1:1 接受持续的 pirtobrutinib 单药治疗或 BendaR，根据免疫球蛋白重链基因突变状态和 Rai 分期进行分层。

The primary end point was independent review committee (IRC)-assessed progression-free survival(PFS); secondary end points included overall survival(OS), investigator (INV)-assessed PFS, safety, and tolerability.

主要终点是独立评审委员会（IRC）评估的无进展生存期（PFS）；次要终点包括总生存（OS）、研究者（INV）评估的PFS、安全性和耐受性。

Results

Overall, 282 patients were randomly assigned to receive pirtobrutinib (n = 141) or BendaR (n = 141).

共有282名患者被随机分配接受皮托布鲁替尼（n = 141）或本达拉替尼（n = 141）。

IRC-assessed PFS was significantly improved with pirtobrutinib versus BendaR (hazard ratio[HR], 0.199 [95% CI, 0.107 to 0.367]; P < .0001), and the 24-month PFS rate was 93.4% (95% CI, 87.6 to 96.5) and 70.7% (95% CI, 61.5 to 78.1), respectively.

独立评审委员会（IRC）评估的无进展生存期（PFS）在使用pirtobrutinib与BendaR相比有显著改善（风险比[HR]，0.199 [95% 置信区间，0.107至0.367]；P < .0001），24个月的PFS率分别为93.4%（95% 置信区间，87.6至96.5）和70.7%（95% 置信区间，61.5至78.1）。

INV-assessed PFS similarly favored pirtobrutinib (HR, 0.186 [95% CI, 0.093 to 0.371]).

研究者评估的无进展生存期（PFS）同样倾向于pirtobrutinib（风险比[HR]，0.186 [95% 置信区间，0.093至0.371]）。

Interim analysis of OS favored pirtobrutinib (median follow-up 32 months; HR, 0.257 [95% CI, 0.070 to 0.934]) despite an effective crossover rate of 52.9%.

尽管有效交叉率达到了52.9%，但中期总生存分析结果有利于pirtobrutinib（中位随访时间32个月；风险比，0.257 [95% 置信区间，0.070至0.934]）

In patients receiving pirtobrutinib versus BendaR: adverse event(AE)-related dose reductions occurred in 3.6% versus 31.1% of patients; grade ≥3 treatment-emergent AEs (TEAEs) occurred in 40.0% versus 67.4% of patients; and treatment discontinuations because of TEAEs occurred in 4.3% versus 15.2% of patients, respectively.

在接受pirtobrutinib与BendaR治疗的患者中：与不良事件（AE）相关的剂量减少发生在3.6%与31.1%的患者中；3级或更高级别的治疗相关不良事件（TEAEs）发生在40.0%与67.4%的患者中；因TEAEs导致的治疗中断发生在4.3%与15.2%的患者中。

Conclusions

Pirtobrutinib demonstrated superiority over BendaR in IRC-assessed PFS in treatment-naïve CLL/SLL.

Pirtobrutinib 在治疗初治CLL/SLL患者中，经IRC评估的无进展生存期（PFS）优于BendaR。

OS trends favored pirtobrutinib despite the study design allowing for crossover.

尽管研究设计允许交叉，但总生存（OS）趋势仍倾向于pirtobrutinib。

Pirtobrutinib was well tolerated, consistent with its known safety profile, and more favorable than BendaR.

Pirtobrutinib的耐受性良好，与其已知的安全性特征一致，并且比BendaR更为有利。