硼替佐米与伏立诺他治疗套细胞淋巴瘤和弥漫性大B细胞淋巴瘤的II期试验
A Phase II Trial of Bortezomib and Vorinostat in Mantle Cell Lymphoma and Diffuse Large B-cell Lymphoma.
作者信息
Yazbeck Victor, Shafer Danielle, Perkins Edward B, Coppola Domenico, Sokol Lubomir, Richards Kristy L, Shea Thomas, Ruan Jia, Parekh Samir, Strair Roger, Flowers Christopher, Morgan David, Kmieciak Maciej, Bose Prithviraj, Kimball Amy, Badros Ashraf Z, Baz Rachid, Lin Hui-Yi, Zhao Xiuhua, Reich Richard R, Tombes Mary Beth, Shrader Ellen, Sankala Heidi, Roberts John D, Sullivan Daniel, Grant Steven, Holkova Beata
机构信息
Massey Cancer Center, Virginia Commonwealth University, Richmond, VA.
Massey Cancer Center, Virginia Commonwealth University, Richmond, VA; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA.
出版信息
Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):569-575.e1. doi: 10.1016/j.clml.2018.05.023. Epub 2018 Jun 6.
BACKGROUND
The proteasome inhibitor bortezomib has demonstrated marked preclinical activity when combined with the histone deacetylase inhibitor vorinostat in leukemia, multiple myeloma, and mantle cell lymphoma (MCL) cells. The present study evaluated the efficacy and safety of the combination in patients with relapsed or refractory MCL and diffuse large B-cell lymphoma (DLBCL).
PATIENTS AND METHODS
The present multicenter, nonrandomized phase II trial used a Simon 2-stage design with 3 cohorts: cohort A, MCL with no previous bortezomib (including untreated MCL); cohort B, MCL with previous bortezomib; and cohort C, relapsed or refractory DLBCL with no previous bortezomib. Vorinostat (400 mg) was administered orally on days 1 to 5 and 8 to 12 before bortezomib (1.3 mg/m), which was administered intravenously on days 1, 4, 8, and 11 of each 21-day cycle.
RESULTS
For the 65 treated patients (22 in cohort A, 4 in cohort B, and 39 in cohort C), the overall response rate was 31.8%, 0%, and 7.7%, respectively. The median progression-free survival was 7.6 months for cohort A and 1.8 months for cohort C. In cohort A, 7 patients had a partial response (PRs), 5 had stable disease (SD), 7 had progressive disease (PD), 1 was not assessed, and 2 were not evaluable. In cohort B, 2 had SD and 2 had PD. In cohort C, 3 had a PR, 8 had SD, 23 had PD, and 5 were not assessed. Baseline NF-κB activation, measured as nuclear RelA by immunohistochemistry, did not correlate with clinical response.
CONCLUSION
The combination of bortezomib and vorinostat is safe and has modest activity in MCL and limited activity in DLBCL.
背景
蛋白酶体抑制剂硼替佐米与组蛋白脱乙酰酶抑制剂伏立诺他联合用于白血病、多发性骨髓瘤和套细胞淋巴瘤（MCL）细胞时，已显示出显著的临床前活性。本研究评估了该联合用药方案用于复发或难治性MCL和弥漫性大B细胞淋巴瘤（DLBCL）患者的疗效和安全性。
患者与方法
本多中心、非随机II期试验采用Simon两阶段设计，分为3个队列：队列A，既往未使用过硼替佐米的MCL（包括未经治疗的MCL）；队列B，既往使用过硼替佐米的MCL；队列C，既往未使用过硼替佐米的复发或难治性DLBCL。在硼替佐米（1.3mg/m²）静脉给药前，于每个21天周期的第1至5天和第8至12天口服伏立诺他（400mg），硼替佐米于每个周期的第1、4、8和11天静脉给药。
结果
65例接受治疗的患者（队列A 22例、队列B 4例、队列C 39例），总缓解率分别为31.8%、0%和7.7%。队列A的中位无进展生存期为7.6个月，队列C为1.8个月。队列A中，7例患者部分缓解（PR），5例病情稳定（SD），7例疾病进展（PD），1例未评估，2例不可评估。队列B中，2例SD，2例PD。队列C中，3例PR，8例SD，23例PD，5例未评估。通过免疫组化测量的基线NF-κB激活（以核RelA表示）与临床反应无关。
结论
硼替佐米与伏立诺他联合用药安全，对MCL有一定活性，对DLBCL活性有限。
Zotero 插件