Munakata Wataru, Kumode Takahiro, Goto Hideki, Fukuhara Noriko, Shimoyama Tatsu, Takeuchi Masahiro, Kawakita Toshiro, Kubo Kohmei, Sawa Masashi, Uchida Toshiki, Mishima Yuko, Ichii Michiko, Hanaya Miyoko, Matsumoto Asuka, Kuriki Masaaki, Seike Toshihiro, Izutsu Koji, Ishizawa Kenichi
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka, Japan.
Br J Haematol. 2025 Feb;206(2):541-550. doi: 10.1111/bjh.19994. Epub 2025 Jan 8.
Zandelisib, a selective, potent PI3Kδ inhibitor, demonstrated favourable outcomes in patients with relapsed or refractory follicular lymphoma in a global phase II study. This phase II study evaluated the efficacy and safety of zandelisib for relapsed or refractory follicular lymphoma or marginal zone lymphoma. Sixty-one patients received zandelisib orally at 60 mg daily continuously in the first two 28-day cycles, followed by intermittent dosing on Days 1-7 following each cycle until progressive disease or unacceptable toxicity. Objective and complete response rates were 75.4% (95% confidence interval [CI], 62.7%-85.5%) and 24.6% (95% CI, 14.5%-37.3%) respectively. Median time to response was 58 days; 70.5% (43/61) of patients achieved their first response by Week 8. At least one Grade ≥ 3 treatment-emergent adverse event (TEAE) occurred in 55.7% of patients: transaminase elevation (8.2%); cutaneous reactions (3.3%); and diarrhoea, enterocolitis and lung infection (1.6% each), defined as adverse events of special interest. The discontinuation rate due to any TEAE was 14.8%. No zandelisib-related death occurred. Zandelisib showed favourable efficacy and tolerability in Japanese patients with relapsed or refractory indolent non-Hodgkin B-cell lymphoma. This unique dosing schedule may maintain efficacy while mitigating the safety issues observed with other PI3Kδ inhibitors (ClinicalTrials.gov number, NCT04533581).
赞德莱西布是一种选择性强效PI3Kδ抑制剂，在一项全球II期研究中，复发或难治性滤泡性淋巴瘤患者使用该药显示出良好疗效。这项II期研究评估了赞德莱西布用于复发或难治性滤泡性淋巴瘤或边缘区淋巴瘤的疗效和安全性。61例患者在前两个28天周期中每天口服60毫克赞德莱西布，持续给药，随后在每个周期的第1至7天进行间歇给药，直至疾病进展或出现不可接受的毒性。客观缓解率和完全缓解率分别为75.4%（95%置信区间[CI]，62.7%-85.5%）和24.6%（95%CI，14.5%-37.3%）。中位缓解时间为58天；70.5%（43/61）的患者在第8周时首次出现缓解。55.7%的患者发生至少1次≥3级治疗中出现的不良事件（TEAE）：转氨酶升高（8.2%）；皮肤反应（3.3%）；腹泻、小肠结肠炎和肺部感染（各1.6%），这些被定义为特别关注的不良事件。因任何TEAE导致的停药率为14.8%。未发生与赞德莱西布相关的死亡。赞德莱西布在复发或难治性惰性非霍奇金B细胞淋巴瘤的日本患者中显示出良好的疗效和耐受性。这种独特的给药方案可能在维持疗效的同时减轻其他PI3Kδ抑制剂所观察到的安全性问题（ClinicalTrials.gov编号，NCT04533581）。
