Objective: To investigate the occurrence and development of bortezomib-induced peripheral neuropathy in newly-diagnosed multiple myeloma (MM) patients. Methods: A total of 114 newly-diagnosed MM patients receiving bortezomib based therapeutic regimen at Ruijin Hospital, Ruijin Hospital Northern Branch, Shanghai North Station Hospital and Yangpu Hospital from September 2008 to May 2017 were enrolled. According to treatment response, patients were divided into three groups: Group 1, complete remission (CR) and very good partial response (VGPR), 60 cases; Group 2, partial remission (PR), 20 cases; Group 3, stable disease (SD） and progressive disease (PD), 34 cases. The incidence, influencing factors and subsequent improvement of peripheral neuropathy（PN）after 4 treatment cycles were analyzed. Results: The overall incidence of peripheral neuropathy was 65.8%; and there were 49 cases(43.0%) in group 1, 13 cases (11.4%) in group 2 and 13 cases (11.4%) in group 3. During the 4 treatment cycles, the dose of bortezomib would be regulated if peripheral neuropathy occurred. Dose of bortezomib was compared between 3 groups by using Kruskal-Wallis test, which revealed that there was significant difference in bortezomib dose and efficacy between the 3 groups (P<0.05）. Efficacy of bortezomib was negatively correlated with peripheral neuropathy. Univariate analysis showed that albumin, beta-2 microglobulin, calcium, hemoglobin, platelets, creatinine, lactate dehydrogenase,sex and age were not the risk factors for peripheral neuropathy (correlation coefficient <0.3）. Peripheral neuropathy could be ameliorated when patients were given Vitamin B12 (P<0.05). Conclusions: For newly-daignosed MM patients, the occurrence of PN in the early treatment predicts a better treatment response to bortezomib based therapeutic regimen. Efficacy of bortezomib is negatively correlated with peripheral neuropathy in newly-diagnosed MM patients. The levels of albumin, beta-2 microglobulin, calcium, hemoglobin, platelets, creatinine, lactate dehydrogenase have no correlation with the incidence of peripheral neuropathy. The bortezomib-induced peripheral neuropathy could be reversible with the administration of Vitamin B12.
CAO Yafeng, WANG Jing, GU Jun, LU Hongyu, XUN Jie, LIU Yuanfang, WANG Yan, WANG Jin, CHEN Yu, CHEN Yubao, LI Jiaming, HAO Jie, MI Jianqing, CHEN Mei
. Analysis of peripheral neuropathy following treatment with bortezomib in 114 newly-diagnosed multiple myeloma patients[J]. Journal of Diagnostics Concepts & Practice, 2017
, 16(05)
: 492
-497
.
DOI: 10.16150/j.1671-2870.2017.05.008
[1] Shen Y, Zhou X, Wang Z, et al.Coagulation profiles and thromboembolic events of bortezomib plus thalidomide and dexamethasone therapy in newly diagnosed multiple myeloma[J]. Leuk Res,2011,35(2):147-151.
[2] 陈灏珠. 实用内科学 (下册)[M]. 人民卫生出版社,2001:1884-1889.
[3] 赵冰冰, 王焰, 糜坚青, 等. 硼替佐米为主的化疗方案对改善初治多发性骨髓瘤患者生存的作用[J]. 上海交通大学学报 (医学版),2011,31(12):1793.
[4] Wang YM, Long H, Yang D, et al.Clinical efficacy of cellular immuotherapy combined with bortezomib for the treatment of patients with multiple myeloma[J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi,2017,25(3):818-822.
[5] Bruna J, Udina E, Alé A, et al.Neurophysiological, histological and immunohistochemical characterization of bortezomib-induced neuropathy in mice[J]. Exp Neurol,2010,223(2):599-608.
[6] 张之南, 沈悌. 血液病诊断及疗效标准[M]. 3版.北京:科学出版社,2007:232-235.
[7] US Department of Health and Human Services. Common terminology criteria for adverse events v4. 03[R]. 2010.
[8] Alsina M, Boyce B, Devlin RD, et al.Development of an in vivo model of human multiple myeloma bone disease[J]. Blood,1996,87(4):1495-1501.
[9] Mateos MV, Hernández JM, Hernández MT, et al.Bortezomib plus melphalan and prednisone in elderly untrea-ted patients with multiple myeloma: results of a multicen-ter phase 1/2 study[J]. Blood,2006,108(7):2165-2172.
[10] Ma MH, Yang HH, Parker K, et al.The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents[J]. Clin Cancer Res,2003,9(3):1136-1144.
[11] Mitsiades N, Mitsiades CS, Richardson PG, et al.The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications[J]. Blood,2003,101(6):2377-2380.
[12] Takamatsu Y.Management of proteasome inhibitor-induced peripheral neuropathy[J]. Nihon Rinsho,2015,73(1):137-141.
[13] Meregalli C, Carozzi VA, Sala B, et al.Bortezomib-induced peripheral neurotoxicity in human multiple myeloma-bearing mice[J]. J Biol Regul Homeost Agents,2015, 29(1):115-124.
[14] San Miguel JF, Schlag R, Khuageva NK, et al.Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma[J]. N Engl J Med,2008,359(9):906-917.
[15] Antoine JC, Camdessanché JP.Peripheral nervous system involvement in patients with cancer[J]. Lancet Neurol,2007,6(1):75-86.
[16] Corso A, Mangiacavalli S, Varettoni M, et al.Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients[J]. Leuk Res,2010,34(4):471-474.
[17] Cho J, Kang D, Lee JY, et al.Impact of dose modification on intravenous bortezomib-induced peripheral neuropathy in multiple myeloma patients[J]. Support Care Cancer,2014,22(10):2669-2675.
[18] Dimopoulos MA, Mateos MV, Richardson PG, et al.Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study[J]. Eur J Haematol,2011,86(1):23-31.
[19] Bruna J, Udina E, Alé A, et al.Neurophysiological, histological and immunohistochemical characterization of bortezomib-induced neuropathy in mice[J]. Exp Neurol,2010,223(2):599-608.
[20] Morawska M, Grzasko N, Kostyra M, et al.Therapy-rela-ted peripheral neuropathy in multiple myeloma patients[J]. Hematol Oncol,2015,33(4):113-119.
[21] 王焰, 张赟翔, 范青叶,等. 23例免疫球蛋白D型多发性骨髓瘤的临床诊治经验[J]. 内科理论与实践,2016, 11(3):165-169.
[22] Favis R, Sun Y, van de Velde H, et al. Genetic variation associated with bortezomib-induced peripheral neuropathy[J]. Pharmacogenet Genomics,2011,21(3):121-129.
[23] Yamamoto S, Kawashiri T, Higuchi H, et al.Behavioral and pharmacological characteristics of bortezomib-induced peripheral neuropathy in rats[J]. J Pharmacol Sci,2015,129(1):43-50.
[24] Cavaletti G, Gilardini A, Canta A, et al.Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat[J]. Exp Neurol,2007,204(1):317-325.
[25] Thawani SP, Tanji K, De Sousa EA, et al.Bortezomib-associated demyelinating neuropathy--clinical and pathologic features[J]. J Clin Neuromuscul Dis,2015,16(4):202-209.
[26] Quartu M, Carozzi VA, Dorsey SG, et al.Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve[J]. Biomed Res Int,2014,2014:180428.
[27] Poruchynsky MS, Sackett DL, Robey RW, et al.Proteasome inhibitors increase tubulin polymerization and stabilization in tissue culture cells: a possible mechanism contributing to peripheral neuropathy and cellular toxicity following proteasome inhibition[J]. Cell Cycle,2008,7(7):940-949.
[28] Broyl A, Corthals SL, Jongen JL, et al.Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial[J]. Lancet Oncol,2010,11(11):1057-1065.
[29] Nasu S, Misawa S, Nakaseko C, et al.Bortezomib-induced neuropathy: axonal membrane depolarization precedes development of neuropathy[J]. Clin Neurophysiol,2014, 125(2):381-387.
[30] Broyl A, Corthals SL, Jongen JL, et al.Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial[J]. Lancet Oncol,2010,11(11):1057-1065.
[31] Campo C, da Silva Filho MI, Weinhold N, et al. Bortezomib-induced peripheral neuropathy: A genome-wide association study on multiple myeloma patients[J/OL]. Hematol Oncol.2017-03-20[2017-10-11].https://www.ncbi.nlm.nih.gov/pubmed/28317148.
