Wolfgang Hiddemann and Roswitha Forstpointner, University Hospital, Ludwig Maximilian University Munich, Munich; Jan Dürig, University Hospital Essen, Essen; Michael Herold, HELIOS-Klinikum Erfurt, Erfurt, Germany; Anna Maria Barbui, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Miguel A. Canales, Hospital Universitario la Paz, Madrid, Spain; Paul K. Cannell, Fiona Stanley Hospital, Murdoch, Western Australia; Mark Hertzberg, Prince of Wales Hospital; Judith Trotman, Concord Repatriation General Hospital, University of Sydney, Sydney, New South Wales; John F. Seymour, Royal Melbourne Hospital, and University of Melbourne, Melbourne, Victoria, Australia; Graham P. Collins, Churchill Hospital, Oxford; John Radford, University of Manchester and the Christie National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester; Robert E. Marcus, Kings College Hospital, London, United Kingdom; Magdalena Klanova, Charles University General Hospital, Prague, Czech Republic; Magdalena Klanova, Alis Burciu, Günter Fingerle-Rowson, Marcel Wolbers, and Tina Nielsen, F. Hoffmann-La Roche, Basel, Switzerland; and Kensei Tobinai, National Cancer Center Hospital, Tokyo, Japan.
J Clin Oncol. 2018 Aug 10;36(23):2395-2404. doi: 10.1200/JCO.2017.76.8960. Epub 2018 Jun 1.
Purpose The GALLIUM study ( ClinicalTrials.gov identifier: NCT01332968) showed that obinutuzumab (GA101; G) significantly prolonged progression-free survival (PFS) in previously untreated patients with follicular lymphoma relative to rituximab (R) when combined with cyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P; CHOP); CVP; or bendamustine. This report focuses on the impact of chemotherapy backbone on efficacy and safety. Patients and Methods A total of 1,202 patients with previously untreated follicular lymphoma (grades 1 to 3a), advanced disease (stage III or IV, or stage II with tumor diameter ≥ 7 cm), Eastern Cooperative Oncology Group performance status 0 to 2, and requiring treatment were randomly assigned 1:1 to G 1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375 mg/m on day 1 of each cycle, for six to eight cycles, depending on chemotherapy (allocated nonrandomly by center). Responding patients received G or R for 2 years or until disease progression. Results Baseline Follicular Lymphoma International Prognostic Index risk, bulky disease, and comorbidities differed by chemotherapy. After 41.1 months median follow-up, PFS (primary end point) was superior for G plus chemotherapy (overall hazard ratio [HR], 0.68; 95% CI, 0.54 to 0.87; P = .0016), with consistent results across chemotherapy backbones (bendamustine: HR, 0.63; 95% CI, 0.46 to 0.88; CHOP: HR, 0.72; 95% CI, 0.48 to 1.10; CVP: HR, 0.79; 95% CI, 0.42 to 1.47). Grade 3 to 5 adverse events, notably cytopenias, were most frequent with CHOP. Grade 3 to 5 infections and second neoplasms were most frequent with bendamustine, which was associated with marked and prolonged reductions in T-cell counts. Fatal events were more frequent in patients treated with bendamustine, possibly reflecting differences in patient risk profiles. Conclusion Improved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation.
目的 GALLIUM 研究（ClinicalTrials.gov 标识符：NCT01332968）表明，奥滨尤妥珠单抗（GA101；G）联合环磷酰胺（C）、多柔比星、长春新碱（V）和泼尼松（P；CHOP）；CVP；或苯达莫司汀用于治疗未经治疗的滤泡性淋巴瘤患者时，与利妥昔单抗（R）相比，显著延长了无进展生存期（PFS）。本报告重点关注化疗方案对疗效和安全性的影响。
患者和方法 共纳入 1202 例未经治疗的滤泡性淋巴瘤（1 级至 3a 级）、晚期疾病（III 期或 IV 期，或 II 期且肿瘤直径≥7cm）、东部肿瘤协作组体力状态 0 至 2 分、需要治疗的患者，按 1:1 比例随机分组，分别接受 G 1000mg 于第 1、8 和 15 天的第 1 周期，以及随后周期的第 1 天，或 R 375mg/m 于每个周期的第 1 天，具体取决于化疗方案（根据中心进行非随机分配）。有反应的患者接受 G 或 R 治疗 2 年或直至疾病进展。
结果 基线滤泡性淋巴瘤国际预后指数风险、肿块疾病和合并症因化疗方案而异。中位随访 41.1 个月后，G 联合化疗（主要终点）的 PFS 更优（总风险比 [HR]，0.68；95%CI，0.54 至 0.87；P=0.0016），且在不同化疗方案中结果一致（苯达莫司汀：HR，0.63；95%CI，0.46 至 0.88；CHOP：HR，0.72；95%CI，0.48 至 1.10；CVP：HR，0.79；95%CI，0.42 至 1.47）。最常见的 3 至 5 级不良事件是血液学毒性，尤其是细胞减少症，主要与 CHOP 相关。最常见的 3 至 5 级感染和第二肿瘤是苯达莫司汀相关的，其与显著且持久的 T 细胞计数减少有关。苯达莫司汀治疗的患者中，致命事件更为常见，这可能反映了患者风险特征的差异。
结论 在所有三种化疗方案中，G 联合化疗均观察到 PFS 的改善。安全性特征不同，尽管由于非随机化疗方案的分配，比较结果存在混杂因素。
