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
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
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DOI：
10.1200/jco.2017.73.2784
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发表时间：
2017-11-01
影响因子：
45.3
通讯作者：
de Vos, Sven
中科院分区：
文献类型：
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作者：
Leonard, John P.;Kolibaba, Kathryn S.;de Vos, Sven
目的评价在利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）基础上加用硼替佐米对既往未经治疗的非淋巴中心B细胞样（non-GCB）弥漫性大B细胞淋巴瘤（DLBCL）患者预后的影响。（1：1;按国际预后指数[IPI]评分分层）分为6个21天周期的标准R-CHOP单药治疗或R-CHOP加硼替佐米1.3 mg/m2静脉给药（第1天和第4天）（VR-CHOP）。在183例接受一剂或多剂研究药物治疗的中心确认的非GCB DLBCL患者中评价了主要终点无进展生存期（PFS）结果在中位随访34个月后，25%（R-CHOP）和18%（VR-CHOP）的患者发生了PFS事件，VR-CHOP组PFS的风险比（HR）为0.73（90% CI，0.43 - 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%;高-中等/高IPI患者的2年PFS率分别为65.1%和72.4%（HR，0. 67; 90% CI，0. 34 - 1. 29），低/低-中等IPI患者中为90. 0% vs 88. 9%（HR，0. 85; 90% CI，0. 35 - 2. 10）。R-CHOP和VR-CHOP的总体缓解率分别为98%和96%。总生存率HR为0.75（90% CI，0.38 - 1.45）; 2年生存率分别为88.4%和93.0%。安全性人群中（100例R-CHOP和101例VR-CHOP患者），3级不良事件包括中性粒细胞减少（53% vs 49%），血小板减少症（13%对29%），贫血（7%比15%），白细胞减少症（26%对25%）和神经病变（1%对5%）。前瞻性入组的非GCB DLBCL患者使用R-CHOP比预期更有利，并且通过添加硼替佐米没有显著改善。(C)2017年美国临床肿瘤学会
PurposeTo evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL).Patients and MethodsAfter 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(2) 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).ResultsAfter 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%).ConclusionOutcomes 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. (C) 2017 by American Society of Clinical Oncology