Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Department of Lymphoma, Beijing Cancer Hospital, Peking University, Beijing, 100142, P. R. China.
Cancer Commun (Lond). 2018 May 30;38(1):31. doi: 10.1186/s40880-018-0300-5.
Patients with relapsed/refractory B-cell lymphomas have limited treatment options. GERSHWIN is an open-label, single-arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20 relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e.g., safety, and efficacy and pharmacodynamics).
Patients received 1000 mg obinutuzumab intravenously on days 1, 8, and 15 of cycle 1 (CLL patients; first dose split over 2 days), and on day 1 of cycles 2-8. Each cycle lasted for 21 days; the treatment period was 24 weeks. All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety, efficacy, as well as pharmacodynamics.
A total of 48 patients (> 18 years of age) were enrolled (CLL: 12; DLBCL: 23; FL: 13). The subjects received a median of two lines of anticancer treatment prior to the enrollment. Thirty-five patients (72.9%) had at least one adverse event (AE). The most frequent AE was infusion-related reactions (15 patients; 31.3%), followed by pyrexia (11 patients; 22.9%). Treatment-related AEs were reported in 28 patients (58.3%), and included one death (interstitial lung disease). End-of-treatment (EoT) response rate was 33.3%. Best overall response rate was 47.9%. Most CLL patients achieved a partial response at EoT (58.3%). CD19 depletion occurred in 75.0% of the patients with CLL, and all patients with FL and DLBCL.
The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients; no new safety signals were observed. Clinical trial registration ID NCT01680991.
复发/难治性 B 细胞淋巴瘤患者的治疗选择有限。GERSWHIN 是一项在中国复发/难治性 CD20 滤泡性淋巴瘤（FL）、弥漫性大 B 细胞淋巴瘤（DLBCL）或慢性淋巴细胞白血病（CLL）患者中开展的开放性、单臂、Ib 期奥滨尤珠单抗单药治疗研究。药代动力学的主要研究终点已在之前的报告中报道。我们现在提供次要终点（例如安全性、疗效和药效学）的研究数据。
患者在第 1、8 和 15 天（CLL 患者的第 1 天剂量分 2 天给予）和第 1 天（第 2-8 周期）接受 1000mg 奥滨尤珠单抗静脉输注，每个周期持续 21 天，治疗周期为 24 周。所有至少接受 1 剂奥滨尤珠单抗的患者均纳入安全性、疗效和药效学分析。
共纳入 48 例（年龄>18 岁）患者（CLL：12 例；DLBCL：23 例；FL：13 例）。入组前，受试者接受了中位数为 2 线的抗肿瘤治疗。35 例（72.9%）患者至少发生 1 次不良事件（AE）。最常见的 AE 是输注相关反应（15 例；31.3%），其次是发热（11 例；22.9%）。28 例（58.3%）患者报告治疗相关 AE，包括 1 例死亡（间质性肺病）。治疗结束（EoT）时的缓解率为 33.3%。最佳总体缓解率为 47.9%。大多数 CLL 患者在 EoT 时达到部分缓解（58.3%）。所有 CLL、FL 和 DLBCL 患者的 CD19 均耗竭。
奥滨尤珠单抗单药治疗中国 B 细胞淋巴瘤患者的安全性和疗效与既往非中国患者研究中的观察结果相似，未观察到新的安全性信号。临床试验注册 ID：NCT01680991。
