Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety
Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety
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DOI：
10.1200/jco.2017.76.8960
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发表时间：
2018-08-10
影响因子：
45.3
通讯作者：
Marcus, Robert E.
中科院分区：
文献类型：
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作者：
Hiddemann, Wolfgang;Barbui, Anna Maria;Marcus, Robert E.
目的GALLIUM 研究（ClinicalTrials.gov 标识符：NCT01332968）表明，与环磷酰胺 (C)、阿霉素、长春新碱 (V) 和泼尼松 (P; CHOP) 联合使用时，相对于利妥昔单抗 (R)，obinutuzumab (GA101; G) 显着延长既往未经治疗的滤泡性淋巴瘤患者的无进展生存期 (PFS)；客户副总裁；或苯达莫司汀。本报告重点关注化疗骨干对疗效和安全性的影响。 患者和方法总共 1,202 名患有先前未治疗的滤泡性淋巴瘤（1 至 3a 级）、晚期疾病（III 或 IV 期，或肿瘤直径 7 cm 的 II 期）、东部肿瘤合作组表现状态 0 至 2 且需要治疗的患者被随机分配至周期第 1、8 和 15 天的 G 1,000 mg 组1 和后续周期的第 1 天或每个周期的第 1 天 R 375 mg/m(2)，持续六至八个周期，具体取决于化疗（由中心非随机分配）。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、大块疾病和合并症因化疗而异。中位随访 41.1 个月后，G 加化疗的 PFS（主要终点）优于 G 加化疗（总体风险比 [HR]，0.68；95% CI，0.54 至 0.87；P = 0.0016），各化疗方案的结果一致（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）。 3 至 5 级不良事件，特别是血细胞减少，在 CHOP 中最常见。苯达莫司汀最常见 3 至 5 级感染和继发性肿瘤，这与 T 细胞计数显着且长期的减少有关。在接受苯达莫司汀治疗的患者中，致命事件更为频繁，这可能反映了患者风险状况的差异。 结论 对于所有三种化疗方案，G+化疗均观察到 PFS 改善。尽管非随机化疗分配混淆了比较，但安全性有所不同。
PurposeThe 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 MethodsA 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(2) 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.ResultsBaseline 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.ConclusionImproved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation.