Parsaclisib，一种强效且高度选择性的PI3Kδ抑制剂，已在复发或难治性B细胞恶性肿瘤患者中显示出临床益处。本2期研究(CITADEL-203; NCT03126019, EudraCT 2017-001624-22)评估了Parsaclisib单药治疗复发或难治性滤泡性淋巴瘤(FL)患者的疗效和安全性。18岁以上，经组织学确诊为复发或难治性FL(1-3a级)并曾接受≥2种系统疗法的患者，口服Parsaclisib 20mg/日(QD)治疗8周，然后改为每周一次口服Parsaclisib 20mg(每周给药组[WG])或Parsaclisib 2.5mg/日(QD)治疗(每日给药组[DG])；随后选择DG进行进一步评估。主要终点为客观缓解率(ORR)。在数据截止时(2021年1月15日)，共治疗了126例患者(WG: n = 23; DG: n = 103)。DG的ORR(95%置信区间[CI])为77.7% (68.4-85.3)，完全缓解率(95% CI)为19.4% (12.3-28.4)，中位持续缓解时间(95% CI)为14.7个月 (10.4 - NE)，中位无进展生存期为15.8个月 (11.0 - NE)，中位总生存期尚未达成。所有治疗患者中最常见的任何级别的治疗相关不良事件(TEAEs)包括腹泻(n = 48, 38.1%)，恶心(n = 31, 24.6%)和咳嗽(n = 28, 22.2%)；最常见的≥3级别TEAEs为腹泻(n = 15, 11.9%)，中性粒细胞减少(n = 13, 10.3%)和结肠炎(n = 7, 5.6%)。因治疗相关不良事件而暂停、减量和停药的患者分别占总患者数的46.8%(n = 59)、17.5%(n = 22)和23.8%(n = 30)。Parsaclisib治疗在复发或难治性FL患者中表现出快速持久的反应和良好的安全性。Incyte Corporation。©2023年作者。

Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell malignancies. This phase 2 study (CITADEL-203; NCT03126019, EudraCT 2017-001624-22) assessed efficacy and safety of parsaclisib monotherapy in patients with R/R follicular lymphoma (FL).Patients ≥18 years of age with histologically confirmed R/R FL (grade 1-3a) and prior treatment with ≥2 systemic therapies received parsaclisib 20 mg once daily (QD) for 8 weeks then parsaclisib 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg QD for 8 weeks then parsaclisib 2.5 mg QD (daily dosing group [DG]); DG was selected for further assessment. Primary endpoint was objective response rate (ORR).At data cut-off (January 15, 2021), 126 patients had been treated (WG: n = 23; DG: n = 103). ORR (95% confidence interval [CI]) was 77.7% (68.4-85.3) with a complete response rate (95% CI) of 19.4% (12.3-28.4) in DG; median (95% CI) duration of response was 14.7 months (10.4-not estimable [NE]), median progression-free survival was 15.8 months (11.0-NE), and median overall survival was not reached. The most common any-grade treatment-emergent adverse events (TEAEs) among all treated patients included diarrhoea (n = 48, 38.1%), nausea (n = 31, 24.6%), and cough (n = 28, 22.2%); the most common grade ≥3 TEAEs were diarrhoea (n = 15, 11.9%), neutropenia (n = 13, 10.3%), and colitis (n = 7, 5.6%). Dose interruption, reduction, and discontinuation from TEAEs occurred in 46.8% (n = 59), 17.5% (n = 22), and 23.8% (n = 30) of patients, respectively.Treatment with parsaclisib demonstrated rapid and durable responses, and a manageable safety profile in patients with R/R FL.Incyte Corporation.© 2023 The Authors.