The efficacy and safety of Daratumumab in the treatment of patients with ineligible for stem-cell transplantation and relapsed or refractory multiple myeloma: a Meta-analysis
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摘要: 目的：系统评价Daratumumab治疗新诊断不适合移植及复发难治多发性骨髓瘤（MM）的疗效和安全性，以探索MM新的治疗方案。方法：计算机检索PubMed，Embase，Cochrane Library，OVID，Web of Science，Wanfang，CNKI等电子数据库，检索时限为从建库至2020年11月。收集Daratumumab组对比其他疗法治疗新诊断不适合移植及复发难治MM的随机对照试验。由两位评论员按照Cochrane系统评价的方法，分别进行资料提取、质量评价，并交叉核对，RevMan 5.3软件和Stata 15.1软件进行Meta分析。结果：共纳入5项研究，共2964例MM患者，其中3项研究是关于复发难治MM，纳入1521例患者；2项研究是关于新诊断不适合移植MM，纳入1443例患者。在疗效方面，Daratumumab组较对照组，新诊断不适合移植MM亚组和复发难治MM亚组，严格意义的完全缓解、完全缓解、总反应率、12个月无进展生存时间均明显提高。在安全性方面，Daratumumab组较对照组，新诊断不适合移植MM亚组和复发难治MM亚组，3级及以上的血小板减少发生率、淋巴细胞减少发生率、中性粒细胞减少发生率，上呼吸道感染发生率比较差异均无统计学意义，Daratumumab组输注反应发生率为43%。结论：对于新诊断不适合移植及复发难治MM，Daratumumab组与其他疗法比较，严格意义的完全缓解、完全缓解、总反应率、12个月无进展生存时间均明显提高，3级及以上的血小板减少发生率、淋巴细胞减少发生率、中性粒细胞减少发生率、上呼吸道感染发生率均无明显升高，输注反应发生率较高，但可控。
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关键词:
- 多发性骨髓瘤 /
- Daratumumab /
- 达雷妥尤单抗
Abstract: Objective: To systematically review the efficacy and safety of Daratumumab monoclonal antibody in the treatment of ineligible for stem-cell transplantation and relapsed or refractory multiple myeloma(MM), in order to find effective and safe treatment options for MM patients.Methods: A comprehensive search was conducted until November 2020. Two reviewers collected a randomized controlled trial about Daratumumab in the treatment of patients with ineligible for stem-cell transplantation and relapsed or refractory MM. Revman 5.3 software and Stata 15.1 software were used for statistical analysis.Results: A total of 5 studies were included, with 2964 patients enrolled, 3 studies about relapsed or refractory MM, including 1521 patients, 2 studies about ineligible for stem-cell transplantation MM, including 1443 patients. The results of Meta-analysis showed that the treatment plan with Daratumumab could significantly increase the sCR, CR, ORR, 12 months PFS either relapsed or refractory MM group or ineligible for stem-cell transplantation MM group.There were no significant differences in the degrade ≥ 3 thrombocytopenia rate, the degrade ≥ 3 lymphopenia rate, the degrade ≥ 3 neutropenia rate, and upper respiratory tract infection rate.Conclusion: In ineligible for stem-cell transplantation and relapsed or refractory MM, the treatment plan with Daratumumab is effective and safe.-
Key words:
- multiple myeloma /
- Daratumumab /
- Darzalex
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[1] 中国医师协会血液科医师分会, 中华医学会血液学分会, 中国医师协会多发性骨髓瘤专业委员会.中国多发性骨髓瘤诊治指南(2020年修订)[J].中华内科杂志, 2020, 59(5):314-346.
[2] 谢佳, 吴吕, 陈茜, 等.国产硼替佐米治疗初诊多发性骨髓瘤的临床疗效及安全性研究[J].临床血液学杂志, 2021, 34(5):353-357.
[3] 邱录贵.多发性骨髓瘤的发病与国人特点[J].中国实用内科杂志, 2006, 26(12):886-888.
[4] 朱婉秋, 陈文明.新药时代多发性骨髓瘤的巩固、维持和持续治疗[J].肿瘤研究与临床, 2016, 28(8):561-565.
[5] 李昕, 侯健.单克隆抗体治疗多发性骨髓瘤新进展[J].临床血液学杂志, 2020, 33(7):451-455.
[6] Moher D, Liberati A, Tetzlaff J, et al.Preferred reporting items for systematic reviews and meta-analyses:the PRISMA statement[J].J Clin Epidemiol, 2009, 62(10):1006-1012.
[7] Dimopoulos M, Quach H, Mateos MV, et al.Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma(CANDOR):results from a randomised, multicentre, open-label, phase 3 study[J].Lancet, 2020, 396(10245):186-197.
[8] Dimopoulos MA, Oriol A, Nahi H, et al.Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma[J].N Engl J Med, 2016, 375(14):1319-1331.
[9] Palumbo A, Chanan-Khan A, Weisel K, et al.Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma[J].N Engl J Med, 2016, 375(8):754-766.
[10] Facon T, Kumar S, Plesner T, et al.Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma[J].N Engl J Med, 2019, 380(22):2104-2115.
[11] Mateos MV, Dimopoulos MA, Cavo M, et al.Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma[J].N Engl J Med, 2018, 378(6):518-528.
[12] Lin P, Owens R, Tricot G, et al.Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple Myeloma[J].Am J Clin Pathol, 2004, 121(4):482-488.
[13] de Weers M, Tai YT, van der Veer MS, et al.Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors[J].J Immunol, 2011, 186(3):1840-1848.
[14] Krejcik J, Casneuf T, Nijhof IS, et al.Daratumumab depletes CD381 immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma[J].Blood, 2016, 128(3):384-394.
[15] Nijhof IS, Casneuf T, van Velzen J, et al.CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma[J].Blood, 2016, 128(7):959-970.
[16] Kitadate A, Kobayashi H, Abe Y, et al.Pre-treatment CD38-positive regulatory T cells affect the durable response to daratumumab in relapsed/refractory multiple myeloma patients[J].Haematologica, 2020, 105(1):e37-e40.
[17] Voorhees PM, Kaufman JL, Laubach J, et al.Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma:the GRIFFIN trial[J].Blood, 2020, 136(8):936-945.
[18] Atanackovic D, Luetkens T, Kröger N.Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma[J].Leukemia, 2014, 28(5):993-1000.
[19] Jelinek T, Hajek R.PD-1/PD-L1 inhibitors in multiple myeloma:The present and the future[J].Oncoimmunology, 2016, 5(12):e1254856.
[20] Stocker N, Gaugler B, Ricard L, et al.Daratumumab prevents programmed death ligand-1 expression on antigen-presenting cells in de novo multiple myeloma[J].Cancer Med, 2020, 9(6):2077-2084.
[21] García-Guerrero E, Gogishvili T, Danhof S, et al.Panobinostat induces CD38 upregulation and augments the antimyeloma efficacy of daratumumab[J].Blood, 2017, 129(25):3386-3388.
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