MD Anderson Cancer Center, Houston, TX.
Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland.
J Clin Oncol. 2023 Aug 20;41(24):3988-3997. doi: 10.1200/JCO.23.00562. Epub 2023 May 16.
Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis.
Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety.
The median patient age was 70 years (range, 46-87), the median prior lines of therapy was 3 (range, 1-8), 82.2% had discontinued a prior cBTKi because of disease progression, and 77.8% had intermediate- or high-risk simplified MCL International Prognostic Index score. The ORR was 57.8% (95% CI, 46.9 to 68.1), including 20.0% complete responses (n = 18). At a median follow-up of 12 months, the median DOR was 21.6 months (95% CI, 7.5 to not reached). The 6- and 12-month estimated DOR rates were 73.6% and 57.1%, respectively. In the MCL safety cohort (n = 164), the most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). Grade ≥3 TEAEs of hemorrhage (3.7%) and atrial fibrillation/flutter (1.2%) were less common. Only 3% of patients discontinued pirtobrutinib because of a treatment-related adverse event.
Pirtobrutinib is a first-in-class novel noncovalent (reversible) BTKi and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated R/R MCL. Pirtobrutinib was well tolerated with low rates of treatment discontinuation because of toxicity.
Pirtobrutinib 是一种高选择性、非共价（可逆）布鲁顿酪氨酸激酶抑制剂（BTKi）。我们报告了 pirtobrutinib 在先前接受共价布鲁顿酪氨酸激酶抑制剂（cBTKi）预处理的套细胞淋巴瘤（MCL）患者中的安全性和疗效，这些患者预后较差。
先前接受 cBTKi 治疗的复发/难治性（R/R）MCL 患者在一项多中心 I/II 期试验（BRUIN；ClinicalTrials.gov 标识符：NCT03740529）中接受 pirtobrutinib 单药治疗。在符合主要疗效队列纳入标准的前 90 名连续入组患者中评估疗效。主要终点是总缓解率（ORR）。次要终点包括缓解持续时间（DOR）和安全性。
中位患者年龄为 70 岁（范围，46-87），中位先前治疗线数为 3 条（范围，1-8），82.2%的患者因疾病进展而停用先前的 cBTKi，77.8%的患者具有中高危简化 MCL 国际预后指数评分。ORR 为 57.8%（95%CI，46.9 至 68.1），包括 20.0%的完全缓解（n=18）。在中位随访 12 个月时，中位 DOR 为 21.6 个月（95%CI，7.5 至未达到）。6 个月和 12 个月时的估计 DOR 率分别为 73.6%和 57.1%。在 MCL 安全性队列（n=164）中，最常见的治疗相关不良事件（TEAE）为疲劳（29.9%）、腹泻（21.3%）和呼吸困难（16.5%）。不太常见的是 3.7%的患者出现出血和 1.2%的患者出现心房颤动/扑动的≥3 级 TEAEs。仅有 3%的患者因治疗相关不良事件而停止使用 pirtobrutinib。
Pirtobrutinib 是一种首创的新型非共价（可逆）BTKi，也是首个在先前接受过大量预处理的 R/R MCL 患者中在先前接受 cBTKi 治疗后显示出持久疗效的 BTKi。pirtobrutinib 耐受性良好，因毒性导致停药的发生率较低。
