随机对照 II 期研究：R-CHOP 联合或不联合硼替佐米治疗未经治疗的非生发中心 B 细胞样弥漫性大 B 细胞淋巴瘤患者。
Randomized Phase II Study of R-CHOP With or Without Bortezomib in Previously Untreated Patients With Non-Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma.
机构信息
John P. Leonard, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY; Kathryn S. Kolibaba, Compass Oncology, Vancouver, WA; Kathryn S. Kolibaba and Nicholas J. DiBella, US Oncology Research, The Woodlands; Robert Collins, University of Texas Southwestern Medical Center, Dallas, TX; James A. Reeves, Florida Cancer Specialists, Fort Myers; Julio Hajdenberg, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; Anil Tulpule, Keck Medicine of University of Southern California; Sven de Vos, University of California at Los Angeles Jonsson Comprehensive Cancer Center, Los Angeles; Tatjana Kolevska, Kaiser Permanente Medical Center Northern California, Vallejo; Robert Robles, Bay Area Cancer Research Group (Diablo Valley Medical Group), Pleasant Hill; Andrew Horodner, Cancer Care Associates Medical Group, Redondo Beach, CA; Ian W. Flinn, Sarah Cannon Research Institute, Nashville, TN; Christopher R. Flowers, Winship Cancer Institute of Emory University, Atlanta, GA; Nicholas J. DiBella, Rocky Mountain Cancer Centers, Aurora, CO; Steven W. Papish, Summit Medical Group MD Anderson Cancer Center, Camden, NJ; Parameswaran Venugopal, Rush University Medical Center, Chicago, IL; Amir Tabatabai, York Cancer Center/Cancer Care Associates of York, York, PA; and Jaehong Park, Rachel Neuwirth, George Mulligan, Kaveri Suryanarayan, and Dixie-Lee Esseltine, Millennium Pharmaceuticals, Cambridge, MA.
出版信息
J Clin Oncol. 2017 Nov 1;35(31):3538-3546. doi: 10.1200/JCO.2017.73.2784. Epub 2017 Sep 1.
Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.
目的
评估硼替佐米联合利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）方案对未经治疗的非生发中心 B 细胞样（non-GCB）弥漫性大 B 细胞淋巴瘤（DLBCL）患者结局的影响。
方法
采用 Hans 免疫组化算法实时确定非 GCB DLBCL 后，206 例患者按 1:1 比例（按国际预后指数 [IPI] 评分分层）随机分配至接受 6 个 21 天周期的标准 R-CHOP 方案或 R-CHOP 方案联合硼替佐米 1.3mg/m 静脉注射（第 1 天和第 4 天）（VR-CHOP）。183 例经中心确认的非 GCB DLBCL 患者接受了 1 次或多次研究药物治疗，主要终点无进展生存期（PFS）在此人群中进行评估（91 例 R-CHOP，92 例 VR-CHOP）。
结果
中位随访 34 个月后，R-CHOP 组和 VR-CHOP 组分别有 25%（R-CHOP）和 18%（VR-CHOP）的患者发生 PFS 事件，VR-CHOP 的 PFS 风险比（HR）为 0.73（90%CI，0.43 至 1.24）（P=0.611）。R-CHOP 组和 VR-CHOP 组的 2 年 PFS 率分别为 77.6%和 82.0%；在 IPI 高-中/高危患者中，HR 为 0.67（90%CI，0.34 至 1.29），为 65.1%比 72.4%；在 IPI 低/低-中危患者中，HR 为 0.85（90%CI，0.35 至 2.10），为 90.0%比 88.9%。R-CHOP 和 VR-CHOP 的总缓解率分别为 98%和 96%。总生存 HR 为 0.75（90%CI，0.38 至 1.45）；2 年生存率分别为 88.4%和 93.0%。在安全性人群（100 例 R-CHOP 和 101 例 VR-CHOP 患者）中，≥3 级不良事件包括中性粒细胞减少症（53%比 49%）、血小板减少症（13%比 29%）、贫血（7%比 15%）、白细胞减少症（26%比 25%）和周围神经病变（1%比 5%）。
结论
新诊断的、前瞻性入组的非 GCB DLBCL 患者的结局较 R-CHOP 方案预期更为有利，且添加硼替佐米并未显著改善。
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