Hochster Howard, Weller Edie, Gascoyne Randy D, Habermann Thomas M, Gordon Leo I, Ryan Theresa, Zhang Lijun, Colocci Natalia, Frankel Stanley, Horning Sandra J
New York University Medical Center, New York, NY 10016, USA.
J Clin Oncol. 2009 Apr 1;27(10):1607-14. doi: 10.1200/JCO.2008.17.1561. Epub 2009 Mar 2.
To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma.
Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m(2) once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point.
Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 x 10(-10) [all patients]) and 64% MR v 33% OBS (HR = 0.4; P = 9.2 x 10(-8) [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03).
The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS.
确定在晚期惰性淋巴瘤中，标准化疗后使用利妥昔单抗维持治疗（MR）是否能改善无进展生存期（PFS）。
患有III-IV期惰性淋巴瘤且在接受环磷酰胺、长春新碱和泼尼松（CVP）化疗后病情缓解或稳定的患者，根据初始肿瘤负荷、CVP化疗后的残留疾病（微小或明显）以及组织学进行分层，然后随机分配至观察组（OBS）或接受MR治疗，剂量为375mg/m²，每周1次，共4周，每6个月重复一次，持续2年。PFS为主要终点。
311例（282例为滤泡性淋巴瘤）接受CVP治疗的可评估患者被随机分配至OBS组（n = 158）或MR组（n = 153）。MR组患者的最佳缓解率提高了22%，而OBS组为7%（P = 0.00006）。两个研究组的毒性均极小。随机分组后3年的PFS，MR组为68%，OBS组为33%（风险比[HR] = 0.4；P = 4.4×10⁻¹⁰[所有患者]），滤泡性淋巴瘤患者中，MR组为64%，OBS组为33%（HR = 0.4；P = 9.2×10⁻⁸）。无论滤泡性淋巴瘤国际预后指数评分、肿瘤负荷、残留疾病或组织学情况如何，MR治疗均具有优势。在对MR组患者的多因素分析中，CVP化疗后微小疾病是一个有利的预后因素。3年总生存期（OS），MR组为92%，OBS组为86%（HR = 0.6；对数秩检验单侧P = 0.05），在滤泡性淋巴瘤患者中，MR组为91%，OBS组为86%（HR = 0.6；对数秩检验单侧P = 0.08）。在高肿瘤负荷患者中观察到有利于MR治疗的趋势（对数秩检验单侧P = 0.03）。
E1496研究提供了未经治疗的惰性淋巴瘤的首个III期数据，表明化疗后使用MR可显著延长PFS。
