Offner Fritz, Samoilova Olga, Osmanov Evgenii, Eom Hyeon-Seok, Topp Max S, Raposo João, Pavlov Viacheslav, Ricci Deborah, Chaturvedi Shalini, Zhu Eugene, van de Velde Helgi, Enny Christopher, Rizo Aleksandra, Ferhanoglu Burhan
Department of Hematology, University Hospital Ghent, Ghent, Belgium;
Nizhniy Novgorod Region Clinical Hospital, Nizhniy Novgorod, Russian Federation;
Blood. 2015 Oct 15;126(16):1893-901. doi: 10.1182/blood-2015-03-632430. Epub 2015 Jul 31.
This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871.
这项2期研究评估了在一线利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）治疗中，用硼替佐米替代长春新碱是否能提高非生发中心B细胞样弥漫性大B细胞淋巴瘤（非GCB DLBCL）的疗效，该诊断通过免疫组织化学（汉斯方法）进行中心确认。总共164例患者按1:1随机分组，接受六个21天周期的治疗，其中利妥昔单抗375mg/m²、环磷酰胺750mg/m²和多柔比星50mg/m²均于第1天静脉注射，泼尼松100mg/m²于第1 - 5天口服，另外一组在第1、4、8、11天静脉注射硼替佐米1.3mg/m²（利妥昔单抗、环磷酰胺、多柔比星和泼尼松联合硼替佐米[VR-CAP]；n = 84），另一组在第1天静脉注射长春新碱1.4mg/m²（最大2mg）（R-CHOP；n = 80）。VR-CAP组和R-CHOP组在完全缓解率（64.5%，66.2%；优势比[OR]，0.91；P = 0.80）、总缓解率（93.4%，98.6%；OR，0.21；P = 0.11）、无进展生存期（风险比[HR]，1.12；P = 0.76）或总生存期（HR，0.89；P = 0.75）方面均无显著差异。≥3级不良事件（AE）发生率（88%，89%）、严重AE发生率（38%，34%）、因AE停药率（7%，3%）以及因AE死亡率（2%，5%）在VR-CAP组和R-CHOP组中相似。≥3级周围神经病变发生率分别为6%和3%。在非GCB DLBCL中，VR-CAP组与R-CHOP组相比并未提高疗效。该试验已在www.clinicaltrials.gov上注册，注册号为#NCT01040871。
