硼替佐米治疗多发性骨髓瘤致消化系统自主神经病变相关研究

赵薇薇; 董秀帅; 刘瑶; 高新宇; 李晓云; 常玉莹; 王京华; 戴海滨; 刘娟; 陈丽艳; 王连杰; 王巍

doi:10.13201/j.issn.1004-2806.2022.07.007

硼替佐米治疗多发性骨髓瘤致消化系统自主神经病变相关研究

- 哈尔滨医科大学附属第二医院血液科(哈尔滨，150000)

详细信息

通讯作者: 王巍，E-mail：wangweihmu@qq.com

中图分类号: R733.3

收稿日期: 2022-03-08

刊出日期: 2022-07-01

Study on autonomic neuropathy of digestive system caused by bortezomib in the treatment of multiple myeloma

- Department of Hematology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China

More Information

Corresponding author: WANG Wei, E-mail: wangweihmu@qq.com

Received Date: 08 March 2022

Publish Date: 01 July 2022

摘要

摘要: 目的研究硼替佐米治疗多发性骨髓瘤(MM)致消化系统自主神经病变对临床疗效及生活质量的影响。方法选取2018年1月—2021年12月收治的初诊MM患者150例，接受以硼替佐米为基础的联合方案治疗。观察消化系统自主神经病变的发生率，分析其严重程度与疗效、生存、年龄、基础疾病及个人史的相关性。结果硼替佐米治疗MM致消化系统自主神经病变发生率达60.0%，3级消化系统自主神经病变组总有效率、2年无进展生存率、2年总生存率显著低于1~2级组，差异有统计学意义(P< 0.05)。年龄、便秘、糖尿病、骨折/脊髓压迫卧床及酗酒病史与硼替佐米治疗MM致消化系统自主神经病变发生风险呈正相关(P< 0.05)。经及时调整治疗方案，多数患者消化系统自主神经病变明显减轻，可继续硼替佐米治疗。结论硼替佐米治疗MM致消化系统自主神经病变发生率高，其严重程度与临床疗效、高龄、便秘、糖尿病、骨折/脊髓压迫卧床及酗酒病史密切相关，需早期发现早期处理，以期更好地治疗疾病及逆转自主神经病变。
- 硼替佐米 /
- 多发性骨髓瘤 /
- 消化系统自主神经病变
Abstract: Objective To study the effect of autonomic neuropathy of digestive system caused by bortezomib on the clinical efficacy and quality of life in the treatment of multiple myeloma(MM).Methods A total of 150 patients with newly diagnosed MM admitted from January 2018 to December 2021 were selected to receive bortezomib based combination therapy. The incidence of autonomic neuropathy of the digestive system was observed, and the correlation between the severity and efficacy, survival, age, underlying diseases, and personal history was analyzed.Results The incidence of autonomic neuropathy of digestive system was 60.0%, and the overall response rate, 2-year progression-free and 2-year overall survival of grade 3 autonomic neuropathy of digestive system group were significantly lower than those of grade 1 to 2 group(P< 0.05). The risk of autonomic neuropathy of digestive system was positively correlated with age, constipation, diabetes, bed rest with fracture/spinal cord compression and alcoholism(P< 0.05). The autonomic neuropathy of digestive system was significantly relieved in most patients by timely adjustment of treatment regimen, and bortezomib could be used for the follow-up treatment.Conclusion Bortezomib in the treatment of MM causes a high incidence of autonomic neuropathy in the digestive system, and its severity is closely related to clinical efficacy, age, constipation, diabetes, bed rest with fracture/spinal cord compression and alcoholism. Early detection and treatment should be carried out in order to better treat diseases and reverse autonomic neuropathy.
- bortezomib /
- multiple myeloma /
- autonomic neuropathy of digestive system

HTML全文

表 1 MM患者接受硼替佐米联合治疗后疗效例(%)

组别	例数	CR	VGPR	PR	SD	PD	ORR
1~2级消化系统不良反应组	63	7(11.1)	35(55.6)	18(28.6)	2(3.2)	1(1.6)	60(95.2)
3级消化系统不良反应组	27	0	2(7.4)	15(55.6)	4(14.8)	6(22.2)	17(63.0)

下载: 导出CSV

表 2 90例MM患者消化系统不良反应的分级例(%)

症状	例数	1级	2级	3级
呕吐	11(7.3)	9(6.0)	2(1.3)	0
腹泻	13(8.7)	7(4.7)	3(2.0)	3(2.0)
厌食	17(11.3)	13(8.7)	4(2.7)	0
便秘	21(14.0)	2(1.3)	3(2.0)	16(10.7)
肠梗阻	28(18.7)	11(7.3)	9(6.0)	8(5.3)
合计	90(60.0)	42(28.0)	21(14.0)	27(18.0)

下载: 导出CSV

参考文献(23)

[1]	张义霞, 周敏. 硼替佐米联合来那度胺及地塞米松(VRD)方案和硼替佐米联合沙利度胺及地塞米松(VTD)方案治疗多发性骨髓瘤的临床疗效[J]. 系统医学, 2022, 7(1): 102-105. https://www.cnki.com.cn/Article/CJFDTOTAL-XTYX202201025.htm
[2]	高欣, 解海谊, 王慧涵, 等. 国产与进口硼替佐米治疗多发性骨髓瘤的真实世界疗效、安全性及经济学对比[J]. 现代肿瘤医学, 2022, 30(10): 1821-1825. doi: 10.3969/j.issn.1672-4992.2022.10.021
[3]	左晓佳, 叶丽霖, 冯尽意, 等. 硼替佐米不同给药途径对多发性骨髓瘤周围神经病变的影响[J]. 临床医学研究与实践, 2022, 7(4): 498-500. https://www.cnki.com.cn/Article/CJFDTOTAL-LYLC202106005.htm
[4]	任咏惠, 李丽, 汪梅, 等. 硼替佐米致多发性骨髓瘤患者周围神经病变的研究进展[J]. 实用药物与临床, 2021, 24(6): 196-198. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS202204056.htm
[5]	陆晓萱, 颜晓菁. 硼替佐米诱发周围神经病变发病机制的研究进展[J]. 现代肿瘤医学, 2020, 28(23): 4171-4176. doi: 10.3969/j.issn.1672-4992.2020.23.032
[6]	Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma[J]. Lancet Oncol, 2014, 15(12): e538-e548. doi: 10.1016/S1470-2045(14)70442-5
[7]	Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma[J]. Lancet Oncol, 2016, 17(8): e328-e346. doi: 10.1016/S1470-2045(16)30206-6
[8]	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. https://t.cnki.net/kcms/detail?v=znUxuWmAUtfK98WZyaO76VoQHzrTeR7M6VSieTQtxMrI15sSE7eRIodm9hO8efbsawWct0pb9qpiKJiq631LE6q2FLdJ1r3voB4-k2aOo8wcf7mNwkjM1VG_wuOCHSTr&uniplatform=NZKPT
[9]	叶宇凡, 张林娜, 陈晓玲, 等. 真实世界国产硼替佐米治疗初诊多发性骨髓瘤疗效评价[J]. 临床血液学杂志, 2021, 34(5): 327-331. https://t.cnki.net/kcms/detail?v=znUxuWmAUtdzYABNeEV3JLKUMDev5HqGn86eeaZY2VpY2KYGiDmGe13c_NdHSpzke_Ry6v7QYjtTV-_v5amVHtQNwhMCPDSlpQ2JmBYOs35dJF2QQwpFGaAPc9cBecUs&uniplatform=NZKPT
[10]	Gressin R, Daguindau N, Tempescul A, et al. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma[J]. Haematologica, 2019, 104(1): 138-146. doi: 10.3324/haematol.2018.191429
[11]	Mohty B, EI-Cheikh J, Yakoub-Agha I, et al. Peripheral neuropathy and new treatments for multiple myeloma: background and practieal recommendations[J]. Haematologica, 2010, 95(2): 311-319. doi: 10.3324/haematol.2009.012674
[12]	周靖泳, 王娟, 汤华. 多发性骨髓瘤误诊资料分析[J]. 国际检验医学杂志, 2016, 37(10): 1396-1398. doi: 10.3969/j.issn.1673-4130.2016.10.041
[13]	车英格. 145例初诊多发性骨髓瘤的临床特点及以硼替佐米为主的化疗方案的临床分析[D]. 山东滨州: 滨州医学院, 2019.
[14]	王东方, 施丽婕, 杨强. 以腹胀厌食腰痛为主要表现的多发性骨髓瘤一例[J]. 山西医药杂志, 2014, 43(21): 2602-2603. https://www.cnki.com.cn/Article/CJFDTOTAL-SXYY201421063.htm
[15]	韩鹏. 基于文献和真实世界数据的硼替佐米致周围神经病变分析[D]. 重庆: 重庆医科大学, 2019.
[16]	Fukushima T, Nakamura T, Iwao H, et al. Efficacy and safety of bortezomib plus dexamethasone therapy for refractory or relapsed multiple myeloma: once-weekly administration of bortezomib may reduce the incidence of gastrointestinal adverse events[J]. Anticancer Res, 2011, 31(6): 2297-2302.
[17]	张青兰, 刘玉章, 林德全, 等. 基于硼替佐米治疗的多发性骨髓瘤合并肠梗阻26例临床分析[J]. 中华血液学杂志, 2017, 38(7): 625-627.
[18]	郭曌晋, 杨强. 硼替佐米联合地塞米松治疗多发性骨髓瘤患者的疗效及安全性分析[J]. 基层医学论坛, 2020, 24(22): 3147-3148. https://www.cnki.com.cn/Article/CJFDTOTAL-YXLT202022021.htm
[19]	云娟娟. 低剂量硼替佐米为主的三药联合化疗在老年多发性骨髓瘤的疗效观察[J]. 临床医药文献电子杂志, 2020, 7(73): 146-147.
[20]	Lee SE, Choi K, Han S, et al. Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in multiple myeloma patients receiving bortezomib-containing therapy[J]. Anticancer Drugs, 2017, 28(6): 660-668. doi: 10.1097/CAD.0000000000000506
[21]	Mele G, Coppi MR, Melpignano A, et al. Paralytic ileus following "subcutaneous bortezomib" therapy: focus on the clinical emergency-report of two cases[J]. Clin Exp Med, 2016, 16(1): 99-101. doi: 10.1007/s10238-015-0337-6
[22]	Keating M, Dasanu CA. Strategy to reduce bortezomib-induced paralytic ileus in patients with myeloma and impaired renalfunction[J]. BMJ Case Rep, 2016, 2016: bcr2016217000.
[23]	De Sousa-Amorim E, Revuelta I, Diekmann F, et al. High incidence of paralytic ileus after bortezomib treatment of antibody-mediated rejection in kidney transplant recipients: report of 2 cases[J]. Transplantation, 2015, 99(11): e170-e171. doi: 10.1097/TP.0000000000000930