Department of Hematology, Tohoku University Hospital, Sendai, Japan.
Department of Hematology, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.
Cancer Sci. 2022 May;113(5):1702-1711. doi: 10.1111/cas.15308. Epub 2022 Mar 15.
Parsaclisib, a potent, selective, next-generation PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory B-cell lymphoma. We undertook a phase Ib study (CITADEL-111) evaluating safety, pharmacokinetics, and efficacy of parsaclisib in Japanese patients with relapsed or refractory B-cell malignancies. Patients received oral parsaclisib daily for 8 weeks then once weekly (10-mg dose, n = 3; 20-mg dose, n = 14). Pharmacokinetic samples were collected on days 1, 8, and 15, and efficacy was monitored according to Lugano criteria. At data cut-off (August 14, 2020), 6 patients (35.3%) remained on study treatment and 11 (64.7%) discontinued due to progressive disease (9 [52.9%]) or adverse events (2 [11.8%]). Median duration of treatment was 8.3 (range, 0.3-24.4) months. The most commonly reported nonhematologic adverse events were constipation (6 [35.3%]), nausea, and pyrexia (each 4 [23.5%]). Five patients (29.4%) experienced treatment-emergent new or worsening decreased neutrophils to grade 3 or 4. No treatment-emergent worsening in aminotransferase elevations to grade 3 or 4 were observed. Ten patients (58.8%) required dose interruption and 5 (29.4%) dose reduction. Body weight-normalized parsaclisib exposure was comparable between Japanese and Western patients. Objective response rate was 100% in follicular lymphoma (9 of 9 patients, including complete response in 2 patients [22.2%]) and marginal zone lymphoma (2 of 2 patients), and 16.7% in diffuse large B-cell lymphoma (1 of 6 patients). Results observed in Japanese patients with relapsed or refractory follicular or marginal zone lymphoma support further clinical development of parsaclisib in these patient populations.
帕萨昔布是一种有效的、选择性的、下一代 PI3Kδ 抑制剂，已在复发或难治性 B 细胞淋巴瘤患者中显示出临床获益。我们开展了一项 Ib 期研究（CITADEL-111），评估帕萨昔布在日本复发或难治性 B 细胞恶性肿瘤患者中的安全性、药代动力学和疗效。患者接受每日口服帕萨昔布治疗 8 周，然后每周一次（10mg 剂量，n=3；20mg 剂量，n=14）。在第 1、8 和 15 天采集药代动力学样本，并根据卢加诺标准监测疗效。截至数据截止日期（2020 年 8 月 14 日），6 名患者（35.3%）仍在接受研究治疗，11 名患者（64.7%）因疾病进展（9 名[52.9%]）或不良事件（2 名[11.8%]）而停药。中位治疗持续时间为 8.3 个月（范围，0.3-24.4）。最常见的非血液学不良事件是便秘（6 名[35.3%]）、恶心和发热（各 4 名[23.5%]）。5 名患者（29.4%）出现新的或恶化的 3 或 4 级中性粒细胞减少症。未观察到治疗后转氨酶升高至 3 或 4 级的情况恶化。10 名患者（58.8%）需要中断剂量，5 名患者（29.4%）需要减少剂量。体重归一化的帕萨昔布暴露量在日本患者和西方患者之间具有可比性。滤泡性淋巴瘤（9 例患者中的 9 例，包括 2 例患者的完全缓解[22.2%]）和边缘区淋巴瘤（2 例患者中的 2 例）的客观缓解率为 100%，弥漫性大 B 细胞淋巴瘤（6 例患者中的 1 例）的客观缓解率为 16.7%。在复发或难治性滤泡性或边缘区淋巴瘤的日本患者中观察到的结果支持进一步开发帕萨昔布用于这些患者人群。
