State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Tianjin Institutes of Health Science, Tianjin, China.
Clin Cancer Res. 2023 Apr 14;29(8):1440-1449. doi: 10.1158/1078-0432.CCR-22-2939.
To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments.
Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile.
Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6-87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3-15.9). The median PFS was 13.4 months (95% CI, 11.1-16.7). The 12-month OS rate was 91.4% (95% CI, 82.7-95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%).
Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.
评估新型口服 PI3Kδ 抑制剂在至少接受过两种系统治疗的复发/难治滤泡性淋巴瘤（FL）患者中的疗效和安全性。
入组经组织学证实的复发/难治性 FL 患者，这些患者在接受二线或更多线的系统治疗后出现疾病进展。Linperlisib 以 80mg/天的剂量，每天口服，28 天为一个周期，直至疾病进展或出现不可耐受的毒性。该研究的主要终点是客观缓解率（ORR），次要终点包括缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）、疾病控制率和药物安全性特征。
在 114 例筛查出的复发/难治性 FL 患者中，84 例患者被纳入全分析集（FAS）。84 例 FAS 患者的 ORR 为 79.8%（95%CI，69.6-87.8，67 例），其中 13 例（15.5%）患者达到完全缓解，54 例（64.3%）患者达到部分缓解。DOR 的中位数为 12.3 个月（95%CI，9.3-15.9）。PFS 的中位数为 13.4 个月（95%CI，11.1-16.7）。12 个月 OS 率为 91.4%（95%CI，82.7-95.8），中位 OS 未达到 42 个月。最常见（>3%）的与治疗相关的 3 级及以上不良事件为感染性肺炎（19.0%）、中性粒细胞减少症（15.5%）、淋巴细胞计数减少（4.8%）、白细胞计数减少（4.8%）、脂肪酶升高（3.6%）、血小板计数减少（3.6%）、高甘油三酯血症（3.6%）和间质性肺病（3.6%）。
Linperlisib 为至少接受过两种系统治疗的复发/难治性 FL 患者带来了具有临床意义的疗效和可管理的耐受性。
