From King's College Hospital (R.M.) and the Cancer Research UK and University College London Cancer Trials Centre (E.P., W.T.), London, and the Cancer Research UK Centre, University of Southampton, Southampton (A.D.) - all in the United Kingdom; the Tokai University School of Medicine, Isehara, Japan (K.A.); the University of Kiel, Kiel (W.K.), Gemeinschaftspraxis, Würzburg (R. Schlag), HELIOS Klinikum Erfurt, Erfurt (M.H.), and the Ludwig-Maximilians-University Hospital Grosshadern, Munich (W.H.) - all in Germany; Monash Health and Monash University (S.O.) and the Peter MacCallum Cancer Centre and University of Melbourne (J.F.S.), Melbourne, VIC, Australia; Foothills Medical Centre and Tom Baker Cancer Centre, Calgary, AB (C.O.), and the Cross Cancer Institute, Edmonton, AB (R. Sangha) - both in Canada; Charles University, Prague, Czech Republic (M.T.); and F. Hoffmann-La Roche, Basel, Switzerland (M.W., G.F.-R., K.R., T.M.).
N Engl J Med. 2017 Oct 5;377(14):1331-1344. doi: 10.1056/NEJMoa1614598.
Rituximab-based immunochemotherapy has improved outcomes in patients with follicular lymphoma. Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody. We compared rituximab-based chemotherapy with obinutuzumab-based chemotherapy in patients with previously untreated advanced-stage follicular lymphoma.
We randomly assigned patients to undergo induction treatment with obinutuzumab-based chemotherapy or rituximab-based chemotherapy. Patients with a response received maintenance treatment for up to 2 years with the same antibody that they had received in induction. The primary end point was investigator-assessed progression-free survival.
A total of 1202 patients with follicular lymphoma underwent randomization (601 patients in each group). After a median follow-up of 34.5 months (range, 0 to 54.5), a planned interim analysis showed that obinutuzumab-based chemotherapy resulted in a significantly lower risk of progression, relapse, or death than rituximab-based chemotherapy (estimated 3-year rate of progression-free survival, 80.0% vs. 73.3%; hazard ratio for progression, relapse, or death, 0.66; 95% confidence interval [CI], 0.51 to 0.85; P=0.001). Similar results were seen with regard to independently reviewed progression-free survival and other time-to-event end points. Response rates were similar in the two groups (88.5% in the obinutuzumab group and 86.9% in the rituximab group). Adverse events of grade 3 to 5 were more frequent in the obinutuzumab group than in the rituximab group (74.6% vs. 67.8%), as were serious adverse events (46.1% vs. 39.9%). The rates of adverse events resulting in death were similar in the two groups (4.0% in the obinutuzumab group and 3.4% in the rituximab group). The most common adverse events were infusion-related events that were considered by the investigators to be largely due to obinutuzumab in 353 of 595 patients (59.3%; 95% CI, 55.3 to 63.2) and to rituximab in 292 of 597 patients (48.9%; 95% CI, 44.9 to 52.9; P<0.001). Nausea and neutropenia were common. A total of 35 patients (5.8%) in the obinutuzumab group and 46 (7.7%) in the rituximab group died.
Obinutuzumab-based immunochemotherapy and maintenance therapy resulted in longer progression-free survival than rituximab-based therapy. High-grade adverse events were more common with obinutuzumab-based chemotherapy. (Funded by F. Hoffmann-La Roche; GALLIUM ClinicalTrials.gov number, NCT01332968 .).
基于利妥昔单抗的免疫化疗改善了滤泡性淋巴瘤患者的预后。奥滨尤妥珠单抗是一种糖基化工程的 II 型抗 CD20 单克隆抗体。我们比较了奥滨尤妥珠单抗为基础的化疗与利妥昔单抗为基础的化疗在未经治疗的晚期滤泡性淋巴瘤患者中的疗效。
我们将患者随机分配接受奥滨尤妥珠单抗为基础的化疗或利妥昔单抗为基础的化疗诱导治疗。有反应的患者接受最多 2 年的维持治疗，使用与诱导治疗相同的抗体。主要终点是研究者评估的无进展生存期。
共有 1202 例滤泡性淋巴瘤患者接受了随机分组（每组 601 例）。中位随访 34.5 个月（范围，0 至 54.5）后，计划的中期分析显示，奥滨尤妥珠单抗为基础的化疗显著降低了疾病进展、复发或死亡风险，优于利妥昔单抗为基础的化疗（估计 3 年无进展生存率为 80.0% vs. 73.3%；进展、复发或死亡的风险比为 0.66；95%置信区间[CI]为 0.51 至 0.85；P=0.001）。独立评估的无进展生存期和其他时间相关终点也观察到类似的结果。两组的缓解率相似（奥滨尤妥珠单抗组为 88.5%，利妥昔单抗组为 86.9%）。奥滨尤妥珠单抗组 3 至 5 级不良事件发生率高于利妥昔单抗组（74.6% vs. 67.8%），严重不良事件发生率也高于利妥昔单抗组（46.1% vs. 39.9%）。两组因不良事件导致的死亡率相似（奥滨尤妥珠单抗组为 4.0%，利妥昔单抗组为 3.4%）。最常见的不良事件是输注相关事件，研究者认为 595 例患者中有 353 例（59.3%；95%CI，55.3 至 63.2）和 597 例患者中有 292 例（48.9%；95%CI，44.9 至 52.9；P<0.001）主要归因于奥滨尤妥珠单抗，而归因于利妥昔单抗的分别有 292 例（48.9%；95%CI，44.9 至 52.9；P<0.001）。恶心和中性粒细胞减少症很常见。奥滨尤妥珠单抗组有 35 例（5.8%）和利妥昔单抗组有 46 例（7.7%）患者死亡。
奥滨尤妥珠单抗为基础的免疫化疗和维持治疗可延长无进展生存期，优于利妥昔单抗为基础的治疗。奥滨尤妥珠单抗为基础的化疗更常见的是高级别不良事件。（由 F. Hoffmann-La Roche 资助；GALLIUM 临床试验.gov 编号，NCT01332968）。
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