硼替佐米联合 CHOP-利妥昔单抗方案治疗初治弥漫性大 B 细胞淋巴瘤和套细胞淋巴瘤。

Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma.

机构信息

Center for Lymphoma and Myeloma, Weill Cornell Medical College, 525 East 68th St, Starr 340, New York, NY 10065, USA.

出版信息

J Clin Oncol. 2011 Feb 20;29(6):690-7. doi: 10.1200/JCO.2010.31.1142. Epub 2010 Dec 28.

DOI:10.1200/JCO.2010.31.1142

PMID:21189393

Abstract

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/m(2) (n = 4), 1.0 mg/m(2) (n = 9), or 1.3 mg/m(2) (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.

摘要

目的

蛋白酶体抑制剂硼替佐米可能增强淋巴瘤的化疗免疫治疗活性。我们评估了递增剂量硼替佐米联合标准环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）联合利妥昔单抗（R）在未经治疗的弥漫性大 B 细胞淋巴瘤（DLBCL）和套细胞淋巴瘤（MCL）患者中的疗效。

方法

76 例未经治疗的 DLBCL（n=40）和 MCL（n=36）患者每 21 天接受标准 CHOP（CHOP-21）治疗，同时在第 1 天和第 4 天给予 R 和硼替佐米 0.7mg/m2（n=4）、1.0mg/m2（n=9）或 1.3mg/m2（n=63），共 6 个周期。

结果

中位年龄为 63 岁（范围，20 至 87 岁），国际预后指数（IPI）评分普遍较差（2 分者占 39%，3 至 5 分者占 49%），MCL 患者的套细胞淋巴瘤国际预后指数评分也较差（28%为中危，39%为高危）。毒性可控制，包括 49 例（8%为 2 级，4%为 3 级）周围神经病和 3 级/4 级贫血（13%）、中性粒细胞减少（41%）和血小板减少（25%）。对于 DLBCL，可评估的总缓解率（ORR）为 100%，完全缓解（CR）/未确认完全缓解（CRu）率为 86%（n=35）。意向治疗（ITT，n=40）ORR 为 88%，CR/CRu 率为 75%，2 年无进展生存率（PFS）为 64%（95%CI，47%至 77%），2 年总生存率（OS）为 70%（95%CI，53%至 82%）。对于 MCL，可评估的 ORR 为 91%，CR/CRu 率为 72%（n=32）。ITT（n=36）ORR 为 81%，CR/CRu 率为 64%，2 年 PFS 为 44%（95%CI，27%至 60%），2 年 OS 为 86%（95%CI，70%至 94%）。IPI 和 MIPI 分别与 DLBCL 和 MCL 的生存相关。与单独接受 R-CHOP 治疗的 DLBCL 不同，非生发中心 B 细胞（non-GCB）和 GCB 亚型的结局相似。