文献标题：Bortezomib Plus CHOP-Rituximab for Previously Untreated Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma

文献出处：JCO Dec 28, 2010.doi:10.1200/JCO.2010.31.1142
期刊影响因子:17.793

PMID：21189393

硼替佐米联合R－CHOP使用安全，增强治疗效果，特别是在NGCB DLBCL疾病中，这也证明了随机研究结果。本文在线发表在2010年12月28日的《Journal of Clinical Oncology》。

   蛋白酶体抑制剂硼替佐米可以增强化学免疫疗法对淋巴瘤的治疗作用。本研究旨在评价大剂量硼替佐米加标准环磷酰胺+多柔比星+长春新碱+泼尼松（CHOP）加利妥昔单抗（R）对弥散性大B细胞淋巴瘤（DLBCL）和外套细胞淋巴瘤（MCL）患者的治疗效果。

     76例未治疗过的DLBCL（n=40）和MCL（n=36）患者接受21天为一周期的标准CHOP治疗（CHOP－21），并在第一和第四天联合R加硼替佐米治疗，剂量分别为0.7mg/m(n=4)，1.0mg/m(n=9)，及1.3mg/m (n=63)，共6个周期。

   年龄中位数为63岁（年龄范围，20至87岁），国际预后指数（IPI）评分普遍不良（IPI2为39%，　IPI3-5为49%），MCL患者外套细胞淋巴瘤国际预后指数评分相同（中危28%，高危39%）。毒性可控，包括神经病变49例（2级8%，3级4%），及3－4级贫血（13%）、嗜中性白血球减少症（41%）和血小板减少症（25%）。弥散性大B细胞性淋巴瘤方面，可评价总有效率（ORR）为100%，完全缓解（CR）/不确定完全缓解（CRu）为86%（n=35）。意向-治疗（ITT；n=40）ORR为88%，CR/Cru75%；2年无进展存活（PFS）64%（95%CI，47%－77%），2年总存活（OS）70%（95%CI，53%－82%）。MCL方面，可评价ORR为91%，CR./CRu72% (n=32)。ITT（n=36）ORR为81%，CR/CRu64%，2年PFS为44%（95%CI，27%－60%），2年OS为86%（95%CI，70%－94%）。IPI和MIPI与DLBCL和MCL存活相关。与单用R－CHOP治疗的DLBCL不同，非生发中心B细胞（NGCB）和GCB亚型具有类似结果

医脉通推荐英文摘要
J Clin Oncol. 2010 Dec 28.doi:10.1200/JCO.2010.31.1142

Bortezomib Plus CHOP-Rituximab for Previously Untreated Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma

Jia Ruan, Peter Martin, Richard R. Furman,

（John P. Leonard, MD, Center for Lymphoma and Myeloma, Weill Cornell Medical College, 525 East 68th St, Starr 340, New York）

Purpose The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).

Patients and Methods Seventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.7 mg/m2 (n = 4), 1.0 mg/m2 (n = 9), or 1.3 mg/m2 (n = 63) on days 1 and 4 for six cycles.

Results Median age was 63 years (range, 20 to 87), and International Prognostic Index (IPI) scores were generally unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell Lymphoma International Prognostic Index scores in patients with MCL (28% intermediate risk and 39% high risk). Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu; n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91% with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had similar outcomes.

Conclusion Bortezomib with R-CHOP-21 can be safely administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying randomized studies.

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PRIMA结果公布：利妥昔单抗改善PFS