Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study
Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study
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DOI：
10.1200/jco.2017.76.3656
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发表时间：
2018-08-01
影响因子：
45.3
通讯作者：
Sehn, Laurie H.
中科院分区：
文献类型：
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作者：
Cheson, Bruce D.;Chua, Neil;Sehn, Laurie H.
目的对接受obinutuzumab治疗的利妥昔单抗难治性惰性非霍奇金淋巴瘤患者的随机III期GADOLIN试验进行更新分析（GA 101; G）和苯达莫司汀（B）。患者和方法组织学证实的利妥昔单抗难治性CD 20（+）惰性非霍奇金淋巴瘤患者接受G 1，000 mg（第1周期第1、8和15天;第2至6周期第1天）加B 90 mg/m（2）/d（第1和2天，所有周期）或B 120 mg/m（2）/d单药治疗。未发生G-B疾病进展的患者接受G维持（每2个月1，000 mg）长达2年。主要终点是无进展生存期（PFS）。结果413例随机分配的患者（意向治疗[ITT]：G-B，n = 204; B单药治疗，n = 209），335例滤泡性淋巴瘤（FL; G-B，n = 164; B单药治疗，n = 171）。在中位随访31.8个月后，ITT患者的中位PFS为25.8个月（G-B）和14.1个月（B单药治疗;风险比[HR]，0.57; 95% CI，0.44至0.73; P <0.001）。总生存期（OS）也延长（HR，0.67; 95% CI，0.47 - 0.96; P = 0.027）。FL患者的PFS和OS获益相似。（72.5%）和133 G-B和B单药治疗组分别有65.5%的患者，最常见的是中性粒细胞减少症（G-B，34.8%; B单药治疗，27.1%）、血小板减少（10.8%和15.8%）、贫血（7.4%和10.8%）和输注相关反应（9.3%和3.4%）。89例G-B患者（43.6%）和75例B单药治疗患者（36.9%）发生严重AE; 16例（7.8%）和13例（6.4%）发生致命AE，分别为ConclusionThis更新的分析证实了G-B的PFS获益，主要分析中显示。在ITT人群和FL患者中也证实了显著的OS获益。两种治疗的毒性相似。
PurposeTo perform an updated analysis of the randomized phase III GADOLIN trial in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated with obinutuzumab (GA101; G) and bendamustine (B).Patients and MethodsPatients with histologically documented, rituximab-refractory CD20(+) indolent non-Hodgkin lymphoma received G 1,000 mg (days 1, 8, and 15, cycle 1; day 1, cycles 2 to 6) plus B 90 mg/m(2)/d (days 1 and 2, all cycles) or B 120 mg/m(2)/d monotherapy. Patients who did not experience disease progression with G-B received G maintenance (1,000 mg every 2 months) for up to 2 years. The primary end point was progression-free survival (PFS).ResultsOf 413 randomly assigned patients (intention-to-treat [ITT]: G-B, n = 204; B monotherapy, n = 209), 335 had follicular lymphoma (FL; G-B, n = 164; B monotherapy, n = 171). After a median follow-up of 31.8 months, median PFS in ITT patients was 25.8 months (G-B) and 14.1 months (B monotherapy; hazard ratio [HR], 0.57; 95% CI, 0.44 to 0.73; P < .001). Overall survival (OS) also was prolonged (HR, 0.67; 95% CI, 0.47 to 0.96; P = .027). PFS and OS benefits were similar in patients with FL. Grade 3 to 5 adverse events (AEs) were reported by 148 (72.5%) and 133 (65.5%) patients in the G-B and B monotherapy arms, respectively, most commonly neutropenia (G-B, 34.8%; B monotherapy, 27.1%), thrombocytopenia (10.8% and 15.8%), anemia (7.4% and 10.8%), and infusion-related reactions (9.3% and 3.4%). Serious AEs occurred in 89 G-B patients (43.6%) and 75 B monotherapy patients (36.9%); fatal AEs occurred in 16 (7.8%) and 13 (6.4%), respectively.ConclusionThis updated analysis confirms the PFS benefit for G-B shown in the primary analysis. A substantial OS benefit also was demonstrated in the ITT population and in patients with FL. Toxicity was similar for both treatments.