埃罗妥珠单抗治疗难治性/复发性多发性骨髓瘤临床试验效果的Meta分析

doi:10.5246/jcps.2017.07.059

中国药学(英文版) ›› 2017, Vol. 26 ›› Issue (7): 528-533.DOI: 10.5246/jcps.2017.07.059

• 【药事管理与临床药学专栏】 • 上一篇下一篇

埃罗妥珠单抗治疗难治性/复发性多发性骨髓瘤临床试验效果的Meta分析

张林^1*, 丁洁卫¹, 王阳², 金晓宣³, 葛伟东⁴, 黄淑婷³, 李玉婷³

1. 绍兴市人民医院浙江大学绍兴医院临床药学科, 浙江绍兴 312000
2. Frontage Laboratories, Inc, 700 Pennsylvania Dr, Exton, 美国宾夕法尼亚州 19341
3. 绍兴文理学院化学化工学院药学系, 浙江绍兴 312000
4. 浙江省人民医院超声诊断科, 浙江杭州 310014

收稿日期:2017-03-25 修回日期:2017-04-15 出版日期:2017-07-28 发布日期:2017-04-30
通讯作者: Tel.: +86-18258035799, +86-0575-88228650, E-mail: zl9099@126.com
基金资助:
Zhejiang Public Welfare Technology Application Research Project (Grant No. 2015C33285), Zhejiang Provincial Natural Science Foundation Project (Grant No. LY14H300002), Shaoxing Science and Technology Bureau General Project (Grant No. 2015B70070) and Zhejiang Medical and Health General Research Program (Grant No. 2013KYB030).

A novel drug of elotuzumab for treatment of refractory/relapsed multiple myeloma: a meta-analysis of eight trials

Lin Zhang^1*, Jiewei Ding¹, Yang Wang², Xiaoxuan Jin³, Weidong Ge⁴, Shuting Huang³, Yuting Li³

1. Department of Pharmacy, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000, Zhejiang
2. Frontage Laboratories, Inc, 700 Pennsylvania Dr, Exton, PA 19341, USA
3. School of Pharmacy, College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing 312000, Zhejiang
4. Department of Ultrasonography, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang

Received:2017-03-25 Revised:2017-04-15 Online:2017-07-28 Published:2017-04-30
Contact: Tel.: +86-18258035799, +86-0575-88228650, E-mail: zl9099@126.com
Supported by:
Zhejiang Public Welfare Technology Application Research Project (Grant No. 2015C33285), Zhejiang Provincial Natural Science Foundation Project (Grant No. LY14H300002), Shaoxing Science and Technology Bureau General Project (Grant No. 2015B70070) and Zhejiang Medical and Health General Research Program (Grant No. 2013KYB030).

摘要/Abstract

摘要：

埃罗妥珠单抗在2015年被美国FDA批准成为治疗多发性骨髓瘤的新药后，即成为了多发性骨髓瘤患者的新选择, 该药是治疗多发性骨髓瘤的首个免疫刺激疗法药物, 用于与来那度胺、地塞米松联合治疗复发或难治性的多发性骨髓瘤。目前有8个临床试验是关于埃罗妥珠单抗在治疗多发性骨髓瘤的研究, 因此我们收集现有的临床试验报告分析该药在临床应用上的效果, 以更好地评价该药在难治性/复发性多发性骨髓瘤中的安全性与有效性。检索数据库包括Cochrane、EMBASE、PubMed、Medline; 检索关键字为: “elotuzumab”, “Multiple myeloma”。最后应用R软件对收集到的数据进行Meta分析, 根据文章间的异质性决定使用固定效应模型或者随机效应模型。根据收集到的文献, 筛选并确认8篇总计608例多发性骨髓瘤患者参与的临床试验; 结果应用联合埃罗妥珠单抗方案的608例多发性骨髓瘤患者中总缓解率达到63％, 有162例(26.6%)达到非常满意的部分缓解, 有34例(5.59%)达到了完全缓解。该药最常见的不良反应主要包括贫血、淋巴细胞减少、血小板减少症、中性粒细胞减少症和疲劳等。因此埃罗妥珠单抗联合方案在难治性/复发性多发性骨髓瘤患者中产生了满意的临床效果, 可作为该类患者连续治疗的适宜选择。

关键词: 埃罗妥珠单抗, Meta分析, 难治性/复发性多发性骨髓瘤

Abstract:

Elotuzumab was approved by the US FDA in 2015 as a new drug for the treatment of multiple myeloma (MM), and it became a new choice for MM patients. The drug is the first immunostimulatory drug to treat MM and used to treat recurrent/refractory multiple myeloma (R/RMM) in combination with lenalidomide and dexamethasone. Therefore, we collected the reports from existing clinical trials to analyze the efficacy of the drug in clinical applications to better evaluate the effects of the drug on R/RMM. The search strategy used “elotuzumab” and “multiple myeloma” as keywords to search from the database of Cochrane, Embase, PubMed and Medline. The heterogeneity among the studies was assessed using the Cochrane χ² test, and its extent was evaluated using I² statistics. A P value of less than 0.05 was considered as statistically significant. All meta-analyses were conducted with R Software 3.3.2. We identified eight prospective studies consisting of 608 MM patients. The meta-analysis showed that the overall response rate (ORR) was 63%, 162 patients (26.6%) achieved a very good partial response rate (VGPR), and 34 patients (5.59%) achieved complete response rate (CR). The most common adverse effects of the drug included anemia, lymphopenia, thrombocytopenia, neutropenia and fatigue. Therefore, elotuzumab combination regimens offered clinical benefits to R/RMM patients, and such a combination therapy was a suitable option for continuous treatment for R/RMM patients.

Key words: Elotuzumab, Meta-analysis, Refractory/Relapsed multiple myeloma

中图分类号:

R969.4

Supporting:

张林, 丁洁卫, 王阳, 金晓宣, 葛伟东, 黄淑婷, 李玉婷. 埃罗妥珠单抗治疗难治性/复发性多发性骨髓瘤临床试验效果的Meta分析[J]. 中国药学(英文版), 2017, 26(7): 528-533.

Lin Zhang, Jiewei Ding, Yang Wang, Xiaoxuan Jin, Weidong Ge, Shuting Huang, Yuting Li. A novel drug of elotuzumab for treatment of refractory/relapsed multiple myeloma: a meta-analysis of eight trials[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(7): 528-533.

参考文献

[1] Terpos, E.; International Myeloma, S. Clin. Lymphoma Myeloma Leuk. 2017.

[2] Chan, H.S.H.; Chen, C.I.; Reece, D.E. Curr. Hematol. Malig. Rep. 2017, 12, 96-108.

[3] Zhang, L.; Jin, X.; Huang, S.; Xu, W.; Ding, J. J. Chin. Pharm. Sci. 2017, 26, 222-229.

[4] Jakubowiak, A.; Offidani, M.; Pégourie, B.; De La Rubia, J.; Garderet, L.; Laribi, K.; Bosi, A.; Marasca, R.; Laubach, J.; Mohrbacher, A.; Carella, A.M.; Singhal, A.K.; Tsao, L.C.; Lynch, M.; Bleickardt, E.; Jou, Y.M.; Robbins, M.; Palumbo, A. Blood. 2016, 127, 2833-2840.

[5] Jakubowiak, A.J.; Benson, D.M.; Bensinger, W.; Siegel, D.S.; Zimmerman, T.M.; Mohrbacher, A.; Richardson, P.G.; Afar, D.E.; Singhal, A.K.; Anderson, K.C. J. Clin. Oncol. 2012, 30, 1960-1965.

[6] Lonial, S.; Dimopoulos, M.; Palumbo, A.; White, D.; Grosicki, S.; Spicka, I.; Walter-Croneck, A.; Moreau, P.; Mateos, M.V.; Magen, H.; Belch, A.; Reece, D.; Beksac, M.; Spencer, A.; Oakervee, H.; Orlowski, R. Z.; Taniwaki, M.; Röllig, C.; Einsele, H.; Wu, K.L.; Singhal, A.; San-Miguel, J.; Matsumoto, M.; Katz, J.; Bleickardt, E.; Poulart, V.; Anderson, K.C.; Richardson, P. New England J. Med. 2015, 373, 621-631.

[7] Lonial, S.; Vij, R.; Harousseau, J. L.; Facon, T.; Moreau, P.; Mazumder, A.; Kaufman, J.L.; Leleu, X.; Tsao, L.C.; Westland, C.; Singhal, A.K.; Jagannath, S. J. Clin. Oncol. 2012, 30, 1953-1959.

[8] Mateos, M.V.; Granell, M.; Oriol, A.; Martinez-Lopez, J.; Blade, J.; Hernandez, M.T.; Martín, J.; Gironella, M.; Lynch, M.; Bleickardt, E.; Paliwal, P.; Singhal, A.; San-Miguel, J. British J. Haematology. 2016, 175, 448-456.

[9] Richardson, P.G.; Jagannath, S.; Moreau, P.; Jakubowiak, A.J.; Raab, M.S.; Facon, T.; Vij, R.; White, D.; Reece, D.E.; Benboubker, L.; Zonder, J.; Tsao, L.C.; Anderson, K.C.; Bleickardt, E.; Singhal, A.K.; Lonial, S.; Investigators, S. Lancet. Haematology. 2015, 2, 516-527.

[10] Zonder, J.A.; Mohrbacher, A.F.; Singhal, S.; van Rhee, F.; Bensinger, W.I.; Ding, H.; Fry, J.; Afar, D.E.; Singhal, A.K. Blood. 2012, 120, 552-559.

[11] Iida, S.; Nagai, H.; Kinoshita, G.; Miyoshi, M.; Robbins, M.; Pandya, D.; Bleickardt, E.; Chou, T. Int. J. Hematol. 2017, 105, 326-334.

[12] Podar, K.; Jager, D. Curr. Cancer Drug Targets. 2017, 17, 1-24.

[13] Jung, S.H.; Lee, H.J.; Vo, M.C.; Kim, H.J.; Lee, J.J. Crit. Rev. Oncol. Hematol. 2017, 111, 87-93.

[14] Chung, C. Pharmacotherapy. 2017, 37, 129-143.

[15] Neri, P.; Bahlis, N.J.; Lonial, S. Clin. Cancer Res. 2016, 22, 5959-5965.

[16] Laubach, J.P.; Paba Prada, C.E.; Richardson, P.G.; Longo, D.L. Clin. Pharmacol. Ther. 2017, 101, 81-88.

[17] Friend, R.; Bhutani, M.; Voorhees, P.M.; Usmani, S.Z. Drug Design, Develop. and Therapy. 2017, 11, 893-900.

[18] Magen, H.; Muchtar, E. Therapeutic Advances Hematology. 2016, 7, 187-95.

[19] Balasa, B.; Yun, R.; Belmar, N.A.; Fox, M.; Chao, D.T.; Robbins, M.D.; Starling, G.C.; Rice, A.G. Cancer Immunol. Immunother: CII. 2015, 64, 61-73.

[20] Mantaj, J.; Jackson, P.J.; Rahman, K.M.; Thurston, D.E. Angew Chem. Int. Ed. Engl. 2017, 56, 462-488.

[21] Yao, H.; Jiang, F.; Lu, A.; Zhang, G. Int. J. Mol. Sci. 2016, 17, 194.

[22] Wilkins, O.; Keeler, A. M.; Flotte, T.R. Hum Gene Ther. Methods. 2017, 28, 61-66.

[23] Jaspers, J.E.; Brentjens, R.J. Pharmacol. Ther. doi:10.1016/j.pharmthera.2017.03.012.

埃罗妥珠单抗治疗难治性/复发性多发性骨髓瘤临床试验效果的Meta分析

A novel drug of elotuzumab for treatment of refractory/relapsed multiple myeloma: a meta-analysis of eight trials

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张格第, 刘庚鑫, 晏子友. 基于meta分析和网络药理学理冲汤(丸)治疗癌症的疗效评价及作用机制研究[J]. 中国药学(英文版), 2023, 32(9): 720-735.
[2]	彭词艳, 陈景, 李斯妮, 李健和, 彭六保. 哌柏西利联用来曲唑对比多西他赛联用表柔比星一线治疗晚期乳腺癌的循证药物经济学评价[J]. 中国药学(英文版), 2023, 32(3): 214-222.
[3]	李雅静, 白雅雯, 杜宇, 严长宏, 麻春杰, 孙丽宁, 卜凤跃, 严昊阳. 玉屏风散治疗慢性肾小球肾炎的临床疗效评价及作用机制研究[J]. 中国药学(英文版), 2023, 32(12): 1006-1026.
[4]	李敏, 常路路, 岳向峰, 杜书章. ACEI联合丹参酮治疗肺心病急性加重期的疗效和安全性的meta分析[J]. 中国药学(英文版), 2022, 31(11): 853-865.
[5]	孙颖光, 岳圆圆, 邵杰敏, 高萌, 邓艳茹, 冯运佳. 康复新液与西瓜霜治疗复发性口腔溃疡疗效比较的meta分析[J]. 中国药学(英文版), 2022, 31(10): 761-772.
[6]	覃思蓓, 贾彤, 扶宇, 李俊蕾, 张欣怡, 祝春素, 梁广楷, 聂小燕, 史录文, 崔一民. CYP3A4基因多态性对心脑血管疾病患者氯吡格雷响应影响的Meta分析[J]. 中国药学(英文版), 2021, 30(9): 762-772.
[7]	周祎, 王军, 张龙. 他汀类药物对于COPD患者肺功能影响的荟萃分析[J]. 中国药学(英文版), 2018, 27(4): 281-288.
[8]	肖锐锐, 徐秀琴, 孙磊, 方晓磊, 肖鹏. 降心率药物伊伐布雷定安全性的系统评价[J]. 中国药学(英文版), 2017, 26(5): 379-389.
[9]	张林, 金晓宣, 黄淑婷, 徐雯宇, 丁洁卫. 卡非佐米及其组合药物在治疗多发性骨髓瘤的有效性及安全性分析[J]. 中国药学(英文版), 2017, 26(3): 222-229.
[10]	赵德华, 楚明明, 陈静, 王继生. 吉西他滨标准剂量30分钟快速输注与低剂量延时输注治疗进展期非小细胞肺癌的Meta分析[J]. 中国药学(英文版), 2017, 26(10): 763-770.
[11]	韩茹, 安雅晶, 赵荣生. α-酮酸对慢性肾脏病患者的附加作用: 一项随机对照试验的系统评价和meta分析[J]. 中国药学(英文版), 2017, 26(1): 63-75.
[12]	饶欣, 王长连, 许雄伟, 黄品芳, 王航, 林璐. 盐酸羟考酮缓释片与硫酸吗啡缓释片的临床疗效安全性对比[J]. 中国药学(英文版), 2016, 25(5): 387-394.
[13]	胡琴, 唐惠林, 邵宏. 基于肠促胰素药物治疗2型糖尿病合并非酒精性肝病的疗效和安全性的系统评价和meta分析[J]. 中国药学(英文版), 2016, 25(3): 206-214.
[14]	叶晓春, 董志, 赵春景, 李頔, 钱妍. 西尼地平与L-型钙离子通道阻滞剂对高血压患者肾脏功能影响的meta分析[J]. 中国药学(英文版), 2015, 24(11): 744-753.
[15]	季双敏, 尚德为, 王曦培, 李安宁, 任宇鹏, 李良, 周田彦, 王传跃, 卢炜. 基于meta分析的利培酮群体药代动力学研究及其在中国精神分裂症患者临床治疗药物监测中的预测应用[J]. 中国药学(英文版), 2014, 23(2): 75-82.