Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
Jpn J Clin Oncol. 2020 Dec 16;50(12):1395-1402. doi: 10.1093/jjco/hyaa153.
Idelalisib is an orally administered, highly selective inhibitor of phosphatidylinositol 3-kinase-δ. In this phase 1b study, the safety, tolerability and pharmacokinetics of idelalisib, an oral inhibitor of phosphatidylinositol 3-kinase-δ, were evaluated in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma.
In total, six patients (follicular lymphoma: n = 3, chronic lymphocytic leukemia: n = 3) were enrolled to receive idelalisib 150 mg twice daily.
No dose-limiting toxicities were reported. The most common adverse events were diarrhea (n = 5), gastritis (n = 3), insomnia (n = 3) and pyrexia (n = 3). The most common ≥grade 3 adverse events were diarrhea (n = 2), increased transaminase levels (n = 2) and decreased appetite (n = 2). The maximum idelalisib plasma concentrations (Cmax) were achieved at 2.50 h (range: 1.50-4.00 h). The mean idelalisib plasma concentrations decreased over time but remained detectable in most patients at 12 h. All enrolled patients underwent efficacy evaluation by investigators, and five patients (follicular lymphoma: n = 2, chronic lymphocytic leukemia: n = 3) achieved partial response. The median duration of partial response was 14.5 months (range: 3.7-31.3 months).
Idelalisib 150 mg twice daily was considered tolerable in Japanese patients with follicular lymphoma or chronic lymphocytic leukemia.(Clinical trial registration: NCT02242045).
依鲁替尼是一种口服、高度选择性的磷脂酰肌醇 3-激酶-δ抑制剂。在这项 1b 期研究中,评估了口服磷脂酰肌醇 3-激酶-δ抑制剂依鲁替尼在复发或难治性惰性 B 细胞非霍奇金淋巴瘤日本患者中的安全性、耐受性和药代动力学。
共纳入 6 例患者(滤泡性淋巴瘤:n=3,慢性淋巴细胞白血病:n=3),接受依鲁替尼 150mg,每日 2 次。
未报告剂量限制性毒性。最常见的不良反应为腹泻(n=5)、胃炎(n=3)、失眠(n=3)和发热(n=3)。最常见的≥3 级不良反应为腹泻(n=2)、转氨酶水平升高(n=2)和食欲下降(n=2)。依鲁替尼最大血浆浓度(Cmax)在 2.50 小时(范围:1.50-4.00 小时)达到。依鲁替尼血浆浓度随时间下降,但在 12 小时时仍能在大多数患者中检测到。所有入组患者均由研究者进行疗效评估,5 例患者(滤泡性淋巴瘤:n=2,慢性淋巴细胞白血病:n=3)获得部分缓解。部分缓解的中位持续时间为 14.5 个月(范围:3.7-31.3 个月)。
依鲁替尼 150mg,每日 2 次在日本滤泡性淋巴瘤或慢性淋巴细胞白血病患者中可耐受。(临床试验注册:NCT02242045)。