在这项针对复发/难治性滤泡性淋巴瘤 (FL) 患者的全球 2 期研究中，采用间歇给药方式给予 zandelisib，以减轻每天连续服用口服 PI3Kδ 抑制剂时报告的免疫相关不良事件和感染。在至少两次先前治疗后患有可测量疾病和进展的合格患者接受赞德利西治疗，直到疾病进展或无法耐受。主要疗效终点是客观缓解率（ORR），关键次要疗效终点是缓解持续时间（DOR）。我们报告了 121 名 FL 患者在每天给药 8 周以进行肿瘤减灭后，间歇性给药 zandelisib。先前治疗的中位数为 3 次（范围为 2-8 次），45% 的患者患有难治性疾病。 ORR 为 73%（95% 置信区间 [CI]，63.9-80.4），完全缓解 (CR) 率为 38%（95% CI，29.3-47.3），中位 DOR 为 16.4 个月（95% CI） ，9.5-未达到）。中位随访时间为 14.3 个月（范围 1-30.5），中位无进展生存期为 11.6 个月（95% CI，8.3 - 未达到）。二十一名患者 (17%) 由于不良事件而停止治疗。 3-4 级相关毒性包括 6% 腹泻、5% 肺部感染、3% 结肠炎（通过活检或影像学证实）、3% 皮疹、2% AST 升高和 1% 非感染性肺炎。 Zandelisib 在接受过多次治疗的复发/难治性 FL 患者中取得了较高的持久缓解率。间歇给药导致严重类别相关毒性的发生率相对较低，这支持对赞德利西作为单药以及与惰性 B 细胞恶性肿瘤联合用药的评估。© 2024 作者。约翰·威利 (John Wiley) 出版的 HemaSphere

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2-8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9-80.4), the complete response (CR) rate was 38% (95% CI, 29.3-47.3), and the median DOR was 16.4 months (95% CI, 9.5-not reached). With a median follow-up of 14.3 months (range, 1-30.5), the median progression-free survival was 11.6 months (95% CI, 8.3-not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3-4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies.© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.