Fukuhara Noriko, Yoshida Isao, Ishiguro Takuro, Fujimoto Katsuya, Kuroda Junya, Uchida Toshiki, Yamamoto Ryusuke, Ogawa Yoshiaki, Hiramatsu Yasushi, Ito Toshiro, Katagiri Seiichiro, Nakazato Tomonori, Suzukawa Kazumi, Kinami Kenzo, Zhou Mi, Negoro Eiju
Tohoku University Hospital, Sendai, Japan.
NHO Shikoku Cancer Center, Matsuyama, Japan.
Cancer Sci. 2025 Aug;116(8):2189-2197. doi: 10.1111/cas.70046. Epub 2025 May 14.
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in Japan, the United States, and Western Europe. Parsaclisib is a potent, selective next-generation PI3Kδ inhibitor that has demonstrated clinical efficacy and tolerability in phase II studies of patients with relapsed or refractory (R/R) B-cell NHL, including FL. We report results from CITADEL-213 (NCT04434937), a phase II study evaluating the efficacy and safety of parsaclisib in Japanese patients with R/R FL. Eligible patients were aged ≥ 18 years with histologically confirmed R/R FL (grade 1, 2, or 3a), had received two or more prior systemic therapies, and were ineligible for hematopoietic stem cell transplantation. Patients received parsaclisib 20 mg once daily for 8 weeks, followed by parsaclisib 2.5 mg once daily thereafter. The primary endpoint was the objective response rate (ORR). At the data cut-off (February 16, 2023), 42 patients had received treatment with parsaclisib, of whom 41 were evaluable for change in target tumor size. Median (range) age at baseline was 66.5 (52-87) years. ORR (95% confidence interval [CI]) was 88.1% (74.4-96.0), with 10 patients (23.8%) experiencing a complete response and 27 patients (64.3%) experiencing a partial response. Median (95% CI) duration of response was not reached (8.0 months-not estimable). The most common treatment-emergent adverse events (TEAEs) were diarrhea (28.6%; grade ≥ 3, 7.1%) and stomatitis (23.8%; grade ≥ 3, 11.9%); TEAEs led to parsaclisib discontinuation in five patients (11.9%). There were no fatal TEAEs. In conclusion, parsaclisib monotherapy demonstrated durable responses with a manageable safety profile in Japanese patients with R/R FL. Trial Registration: ClinicalTrials.gov, NCT04434937.
滤泡性淋巴瘤（FL）是日本、美国和西欧非霍奇金淋巴瘤（NHL）中第二常见的亚型。帕萨克利西布是一种强效、选择性的新一代PI3Kδ抑制剂，在复发或难治性（R/R）B细胞NHL（包括FL）患者的II期研究中已证明具有临床疗效和耐受性。我们报告了CITADEL-213（NCT04434937）的结果，这是一项评估帕萨克利西布对日本R/R FL患者疗效和安全性的II期研究。符合条件的患者年龄≥18岁，组织学确诊为R/R FL（1、2或3a级），既往接受过两种或更多种全身治疗，且不符合造血干细胞移植条件。患者接受帕萨克利西布20mg每日一次，共8周，之后接受帕萨克利西布2.5mg每日一次。主要终点是客观缓解率（ORR）。在数据截止日期（2023年2月16日），42例患者接受了帕萨克利西布治疗，其中41例可评估靶肿瘤大小变化。基线时的中位（范围）年龄为66.5（52 - 87）岁。ORR（95%置信区间[CI]）为88.1%（74.4 - 96.0），10例患者（23.8%）达到完全缓解，27例患者（64.3%）达到部分缓解。中位（95%CI）缓解持续时间未达到（8.0个月 - 不可估计）。最常见的治疗中出现的不良事件（TEAE）为腹泻（28.6%；≥3级，7.1%）和口腔炎（23.8%；≥3级，11.9%）；TEAE导致5例患者（11.9%）停用帕萨克利西布。没有致命的TEAE。总之，帕萨克利西布单药治疗在日本R/R FL患者中显示出持久的缓解效果，且安全性可控。试验注册：ClinicalTrials.gov，NCT04434937。
