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Annals of Hematology

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25.10.2019 | Original Article

Peripheral neuropathy following bortezomib therapy in multiple myeloma patients: association with cumulative dose, heparanase, and TNF-α

verfasst von: Weiwei Zhao, Wei Wang, Xiaoyun Li, Yijun Liu, Haiyan Gao, Yongfang Jiang, Ying Wang

Erschienen in: Annals of Hematology | Ausgabe 12/2019

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Abstract

Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite bortezomib is a promising new generation of drugs for MM, its clinical use is limited by peripheral neurotoxicity in the vast majority of patients, which can be severe and require a reduction of dose or even treatment withdrawal. Tumor necrosis factor-α (TNF-α), as the most important inflammatory factor, could induce the inflammatory response and expression of heparanase (HPSE), which may play a crucial role in peripheral neuropathy after chemotherapy. However, the role of TNF-α in bortezomib-induced peripheral neuropathy (BIPN) has not been reported. In this study, treatment-emergent neuropathy was assessed by total neuropathy score and electrophysiological examination. The expression level of TNF-α and HPSE were evaluated by enzyme-linked immunosorbent assay. The effects of anti-TNF-α on the evolution of neuropathy were tested in rat models of neurotoxicity. The results indicated that with the augment of cumulative dose of bortezomib, the incidence of neuropathy was increased. Moreover, bortezomib administration induced the expression of TNF-α. With the increased expression of TNF-α, neuropathy was exacerbated. TNF-α-induced expression of HSPE was secondary to the development of neuropathy. Co-administration of anti-TNF-α in bortezomib therapy has a potential neuroprotective effect on BIPN in rats. TNF-α participates in the pathogenesis of BIPN, which represents an attractive target for future therapeutic intervention.

Kim K, Lee JH, Kim JS, Min CK, Yoon SS, Shimizu K, Chou T, Kosugi H, Suzuki K, Chen W, Hou J, Lu J, Huang XJ, Huang SY, Chng WJ, Tan D, Teoh G, Chim CS, Nawarawong W, Siritanaratkul N, Durie BG (2014) Clinical profiles of multiple myeloma in Asia-An Asian Myeloma Network study. Am J Hematol 89:751–756. https://doi.org/10.1002/ajh.23731 CrossRefPubMed

Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC (2004) A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 127(2):165–172. https://doi.org/10.1111/j.1365-2141.2004.05188.x CrossRefPubMed

Lonial S (2005) Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood 106(12):3777–3784. https://doi.org/10.1182/blood-2005-03-1173 CrossRefPubMedPubMedCentral

Koeppen S (2014) Treatment of multiple myeloma: thalidomide-, bortezomib-, and lenalidomide-induced peripheral neuropathy. Oncol Res Treat 37(9):506–513. https://doi.org/10.1159/000365534 CrossRefPubMed

Voorhees PM, Dees EC, O’Neil B, Orlowski RZ (2003) The proteasome as a target for cancer therapy. Clin Cancer Res 17(9):6316–6325

Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM, Hulin C, Benboubker L, Fuzibet JG, Renaud M, Moreau P, Avet-Loiseau H (2006) Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 91(11):1498–1505. https://doi.org/10.1200/jco.2005.23.16_suppl.6653 CrossRefPubMed

Jagannath S, Durie BGM, Wolf J, Camacho E, Irwin D, Lutzky J, McKinley M, Gabayan E, Mazumder A, Schenkein D, Crowley J (2005) Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 129(6):776–783. https://doi.org/10.1111/j.1365-2141.2005.05540.x CrossRefPubMed

Richardson PG, Briemberg H, Jagannath S, Wen PY, Barlogie B, Berenson J, Singhal S, Siegel DS, Irwin D, Schuster M, Srkalovic G, Alexanian R, Rajkumar SV, Limentani S, Alsina M, Orlowski RZ, Najarian K, Esseltine D, Anderson KC, Amato AA (2006) Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 24:3113–3120. https://doi.org/10.1200/JCO.2005.04.7779 CrossRefPubMed

Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, S. Rajkumar V, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein D, Anderson K (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348(26):2609–2017. https://doi.org/10.1056/NEJMoa030288 CrossRefPubMed

10.

Schlafer D, Shah KS, Panjic EH, Lonial S (2017) Safety of proteasome inhibitors for treatment of multiple myeloma. Expert Opin Drug Saf 16(2):167–183. https://doi.org/10.1080/14740338.2017.1259310 CrossRefPubMed

11.

Mohty B, El-Cheikh J, Yakoub-Agha I, Moreau P, Harousseau JL, Mohty M (2010) Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations. Haematologica 95:311–319. https://doi.org/10.3324/haematol.2009.012674 CrossRefPubMedPubMedCentral

12.

Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, Palumbo A (2010) Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 116(23):4745–4753. https://doi.org/10.1182/blood-2010-07-294983 CrossRefPubMed

13.

Argyriou AA, Iconomou G, Kalofonos HP (2008) Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 112(5):1593–1599. https://doi.org/10.1182/blood-2008-04-149385 CrossRefPubMed

14.

Cavaletti G, Jakubowiak AJ (2010) Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent study. Leuk Lymphoma 51:1178–1187. https://doi.org/10.3109/10428194.2010.483303 CrossRefPubMed

15.

Oriol A, Giraldo P, Kotsianidis I, Couturier C, Olie R, Angermund R, Corso A (2014) Efficacy and safety of bortezomib-based retreatment at the first relapse in multiple myeloma patients: A retrospective study. Hematology 20(7):405–409. https://doi.org/10.1179/1607845414Y.0000000218 CrossRefPubMed

16.

San-Miguel JF, Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau J, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Bladé J, Boccadoro M, Cavenagh JD, Neuwirth R, Boral AL, Esseltine D, Anderson KC (2008) Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study. Leukemia 22(4):842–849. https://doi.org/10.1038/sj.leu.2405087 CrossRefPubMed

17.

Mateos MV, Richardson PG, Dimopoulos MA, Palumbo A, Anderson KC, Shi H, Elliott J, Dow E, van de Velde H, Niculescu L, San Miguel JF (2015) Effect of cumulative bortezomib dose on survival in multiple myeloma patients receiving bortezomib-melphalan-prednisone in the phase III VISTA study. Am J Hematol 90(4):314–319. https://doi.org/10.1002/ajh.23933 CrossRefPubMed

18.

Mateos MV, Bringhen S, Richardson PG, Lahuerta JJ, Larocca A, Oriol A, Boccadoro M, Garcia-Sanz R, Di Raimondo F, Esseltine DL, van de Velde H, Desai A, Londhe A, San Miguel JF, Palumbo A (2014) Bortezomib cumulative dose, efficacy, and tolerability with three different bortezomib-melphalan-prednisone regimens in previously untreated myeloma patients ineligible for high-dose therapy. Haematologica 99(6):1114–1122. https://doi.org/10.3324/haematol.2013.099341 CrossRefPubMedPubMedCentral

19.

Watanabe T, Mitsuhashi M, Sagawa M, Ri M, Suzuki K, Abe M, Ohmachi K, Nakagawa Y, Nakamura S, Chosa M, Iida S, Kizaki M (2013) Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced peripheral neuropathy for multiple myeloma patients. Blood Cancer J 3(10):e150. https://doi.org/10.1038/bcj.2013.47 CrossRefPubMedPubMedCentral

20.

Carozzi VA, Renn CL, Bardini M, Fazio G, Chiorazzi A, Meregalli C, Oggioni N, Shanks K, Quartu M, Serra MP, Sala B, Cavaletti G, Dorsey SG (2013) Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse. PLoS One 8(9):e72995. https://doi.org/10.1371/journal.pone.0072995 CrossRefPubMedPubMedCentral

21.

Gosselin D, Rivest S (2007) Role of IL-1 and TNF in the brain: twenty years of progress on a Dr. Jekyll/Mr. Hyde duality of the innate immune system. Brain Behav Immun 21(3):281–289. https://doi.org/10.1016/j.bbi.2006.12.004 CrossRefPubMed

22.

Xu Q, Yaksh TL (2011) A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr Opin Anaesthesiol 24(4):400–407. https://doi.org/10.1097/ACO.0b013e32834871df CrossRefPubMedPubMedCentral

23.

Chen G, Wang D, Vikramadithyan R, Yagyu H, Saxena U, Pillarisetti S, Goldberg IJ (2004) Inflammatory cytokines and fatty acids regulate endothelial cell heparanase expression. Biochemistry 43(17):4971–4977. https://doi.org/10.1021/bi0356552 CrossRefPubMed

24.

Lerner I, Hermano E, Zcharia E, Rodkin D, Bulvik R, Doviner V, Rubinstein AM, Ishai-Michaeli R, Atzmon R, Sherman Y, Meirovitz A, Peretz T, Vlodavsky I, Elkin M (2011) Heparanase powers a chronic inflammatory circuit that promotes colitis-associated tumorigenesis in mice. J Clin Invest 121(5):1709–1721. https://doi.org/10.1172/JCI43792 CrossRefPubMedPubMedCentral

25.

Chen S, He Y, Hu Z, Lu S, Yin X, Ma X, Lv C, Jin G (2017) Heparanase mediates intestinal inflammation and injury in a mouse model of sepsis. J Histochem Cytochem 65(4):241–249. https://doi.org/10.1369/0022155417692536 CrossRefPubMedPubMedCentral

26.

Myers RR, Campana WM, Shubayev VI (2006) The role of neuroinflammation in neuropathic pain: mechanisms and therapeutic targets. Drug Discov Today 11(1-2):8–20. https://doi.org/10.1016/S1359-6446(05)03637-8 CrossRefPubMed

27.

Wang Q, Zheng Q, Tan H, Zhang B, Li X, Yang Y, Yu J, Liu Y, Chai H, Wang X, Sun Z, Wang J, Zhu S, Wang F, Yang M, Guo C, Wang H, Zheng Q, Li Y, Chen Q, Zhou A, Tang T (2016) TMCO1 is an ER Ca²⁺ load-activated Ca²⁺ channel. Cell 165(6):1454–1466. https://doi.org/10.1016/j.cell.2016.04.051 CrossRefPubMed

28.

Strauss SJ, Maharaj L, Hoare S, Johnson PW, Radford JA, Vinnecombe S, Millard L, Rohatiner A, Boral A, Trehu E, Schenkein D, Balkwill F, Joel SP, Lister TA (2006) Bortezomib therapy in patients with relapsed or refractory lymphoma: potential correlation of in vitro sensitivity and tumor necrosis factor alpha response with clinical activity. J Clin Oncol 24(13):2105–2112. https://doi.org/10.1200/JCO.2005.04.6789 CrossRefPubMed

29.

Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BGM, Dimopoulos MA, Landgren O, Miguel JFS, Richardson P, Sonneveld P, Rajkumar SV (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125:2068–2074. https://doi.org/10.1182/blood-2014-12-615187 CrossRefPubMedPubMedCentral

30.

Kumar SK, Laubach JP, Giove TJ, Quick M, Neuwirth R, Yung G, Rajkumar SV, Richardson PG (2017) Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. Br J Haematol 178:756–763. https://doi.org/10.1111/bjh.14754 CrossRefPubMed

31.

Richardson PG, Xie W, Mitsiades C, Chanan-Khan AA, Lonial S, Hassoun H, Avigan DE, Oaklander AL, Kuter DJ, Wen PY, Kesari S, Briemberg HR, Schlossman RL, Munshi NC, Heffner LT, Doss D, Esseltine DL, Weller E, Anderson KC, Amato AA (2009) Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol 27:3518–3525. https://doi.org/10.1200/JCO.2008.18.3087 CrossRefPubMedPubMedCentral

32.

Delforge M, Bladé J, Dimopoulos MA, Facon T, Kropff M, Ludwig H, Palumbo A, Damme PV, San-Miguel JF, Sonneveld P (2010) Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol 11(11):1086–1095. https://doi.org/10.1016/S1470-2045(10)70068-1 CrossRefPubMed

33.

Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste A, Díaz-Mediavilla J, Hernández MT, Arriba F, Gutiérrez NC, Martín-Ramos L, Cibeira T, Mateos V, Martínez J, Alegre A, Lahuerta JJ, Miguel JS, Bladé J (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 120:1589–1596. https://doi.org/10.1182/blood-2012-02-408922 CrossRefPubMed

34.

Chng WJ, Dispenzieri A, Chim CS, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, Miguel JS, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H (2014) IMWG consensus on risk stratification in multiple myeloma. Leukemia 28(2):269–277. https://doi.org/10.1038/leu.2013.247 CrossRefPubMed

35.

Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P (2016) Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 375(8):754–766. https://doi.org/10.1056/NEJMoa1606038 CrossRefPubMed

36.

Matsuoka A, Mitsuma A, Maeda O, Kajiyama H, Kiyoi H, Kodera Y, Nagino M, Goto H, Ando Y (2016) Quantitative assessment of chemotherapy-induced peripheral neurotoxicity using a point-of-care nerve conduction device. Cancer Sci 107(10):1453–1457. https://doi.org/10.1111/cas.13010 CrossRefPubMedPubMedCentral

37.

Hideshima T, Chauhan D, Schlossman R, Richardson P, Anderson KC (2001) The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene 20(33):4519–4527. https://doi.org/10.1038/sj.onc.1204623 CrossRefPubMed

38.

Blich M, Golan A, Arvatz G, Sebbag A, Shafat I, Sabo E, Cohen-Kaplan V, Petcherski S, Avniel-Polak S, Eitan A, Hammerman H, Aronson D, Axelman E, Ilan N, Nussbaum G, Vlodavsky I (2013) Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression. Arterioscler Thromb Vasc Biol 2(33):e56–e65. https://doi.org/10.1161/ATVBAHA.112.254961 CrossRef

39.

Chiorazzi A, Canta A, Meregalli C, Carozzi V, Sala B, Oggioni N, Monbaliu J, Velde H, Cavaletti G (2013) Antibody against tumor necrosis factor-α reduces bortezomib-induced allodynia in a rat model. Anticancer Res 33:5453–5460PubMed

40.

Cavaletti G, Gilardini A, Canta A, Rigamonti L, Rodriguez-Menendez V, Ceresa C, Marmiroli P, Bossi M, Oggioni N, D’Incalci M, Coster RD (2007) Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat. Exp Neurol 204:317–325. https://doi.org/10.1016/j.expneurol.2006.11.010 CrossRefPubMed

41.

Meregalli C, Canta A, Carozzi VA, Chiorazzi A, Oggioni N, Gilardini A, Ceresa C, Avezza F, Crippa L, Marmiroli P, Cavaletti G (2010) Bortezomib-induced painful neuropathy in rats: a behavioral, neurophysiological and pathological study in rats. Eur J Pain 14(4):343–350. https://doi.org/10.1016/j.ejpain.2009.07.001 CrossRefPubMed

42.

Cavaletti G, Cavalletti E, Montaguti P, Oggioni N, Negri DO, Tredici G (1997) Effect on the peripheral nervous system of the short-term intravenous administration of paclitaxel in the rat. Neurotoxicology 1(18):137–145

43.

Cavaletti G, Cavalletti E, Oggioni N, Sottani C, Minoia C, D’Incalci M, Zucchetti M, Marmiroli P, Tredici G (2000) Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology 3(21):389–393. https://doi.org/10.1046/j.1529-8027.2001.01008-5.x CrossRef

44.

Ravaglia S, Corso A, Piccolo G, Lozza A, Alfonsi E (2008) Immune-mediated neuropathies in myeloma patients treated with bortezomib. Clin Neurophysiol 119:2507–2512. https://doi.org/10.1016/j.clinph.2008.08.007 CrossRefPubMed

45.

Catterall WA (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev 57(4):411–425. https://doi.org/10.1124/pr.57.4.5 CrossRefPubMed

46.

Gutter-Kapon L, Alishekevitz D, Shaked Y, Li JP, Aronheim A, Ilan N, Vlodavsky I (2016) Heparanase is required for activation and function of macrophages. Proc Natl Acad Sci U S A 113:E7808–E7817. https://doi.org/10.1073/pnas.1611380113 CrossRefPubMedPubMedCentral

47.

Vlodavsky I, Singh P, Boyango I, Gutter-Kapon L, Elkin M, Sanderson RD, Ilan N (2016) Heparanase: from basic research to therapeutic applications in cancer and inflammation. Drug Resist Updat 29:54–75. https://doi.org/10.1016/j.drup.2016.10.001 CrossRefPubMedPubMedCentral

48.

Ramani VC, Vlodavsky I, Ng M, Zhang Y, Barbieri P, Noseda A, Sanderson RD (2016) Chemotherapy induces expression and release of heparanase leading to changes associated with an aggressive tumor phenotype. Matrix Biol 55:22–34. https://doi.org/10.1016/j.matbio.2016.03.006 CrossRefPubMedPubMedCentral

Titel: Peripheral neuropathy following bortezomib therapy in multiple myeloma patients: association with cumulative dose, heparanase, and TNF-α
verfasst von: Weiwei Zhao
Wei Wang
Xiaoyun Li
Yijun Liu
Haiyan Gao
Yongfang Jiang
Ying Wang
Publikationsdatum: 25.10.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 12/2019
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-019-03816-6

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