Background Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov NCT00790036.

中文翻译：

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高危弥漫性大B细胞淋巴瘤的佐剂依维莫司：PILLAR-2随机III期试验的最终结果。

背景国际预后指数（IPI）≥3的弥漫性大B细胞淋巴瘤（DLBCL）患者对基于利妥昔单抗的一线化疗（R-chemo）一线反应完全缓解（CR）后，复发的风险较高。依维莫司在淋巴瘤中具有单药活性。PILLAR-2旨在通过1年佐剂依维莫司改善无病生存期（DFS）。患者和方法将高危（IPI≥3）DLBCL且经正电子发射断层扫描/计算机断层扫描确认的一线R化疗的CR患者随机分为1年依维莫司10 mg /天或安慰剂。主要终点是DFS。次要终点是总体生存期，淋巴瘤特异性生存期和安全性。结果2009年8月至2013年12月，将742例患者随机分为依维莫司（n = 372）或安慰剂（n = 370）。随访的中位数为50。4个月（范围24.0-76.9）。总体而言，47％的患者≥65岁，男性的50％，IPI为4或5的患者42％。分别完成了依维莫司和安慰剂的IP分别为48％和67％。依维莫司停药与安慰剂停药的主要原因是不良事件（不良事件； 30％对12％）和疾病复发（6％对13％）。与安慰剂相比，依维莫司没有显着改善DFS（危险比0.92； 95％CI 0.69-1.22； P = 0.276）。依维莫司的两年DFS率为77.8％（95％CI 72.7-82.1），安慰剂为77.0％（95％CI 72.1-81.1）。依维莫司常见的3/4级AE包括中性粒细胞减少，口腔炎和CD4淋巴细胞减少。结论佐剂依维莫司不能改善已经接受PET / CT确诊的CR患者的DFS。未来的方法应将靶向药物（例如依维莫司）与R-CHOP合并，而不是在获得CR后作为辅助治疗。ClinicalTrials.gov NCT00790036。