The effect of immunomodulatory drugs on bone metabolism of patients with multiple myeloma

References

• Heider M, Nickel K, Hogner M, et al. Multiple myeloma: molecular pathogenesis and disease evolution. Oncol Res Treat. 2021;44(12):672–681. doi: 10.1159/000520312
   PubMed Web of Science ®Google Scholar
• Terpos E, Zamagni E, Lentzsch S, et al. Treatment of multiple myeloma-related bone disease: recommendations from the bone working group of the international myeloma working group. Lancet Oncol. 2021;22(3):e119–e130. doi: 10.1016/S1470-2045(20)30559-3
   PubMed Web of Science ®Google Scholar
• Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21–33. doi: 10.4065/78.1.21
   PubMed Web of Science ®Google Scholar
• Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple myeloma: a review. JAMA. 2022;327(5):464–477. doi: 10.1001/jama.2022.0003
   PubMed Web of Science ®Google Scholar
• Zhang F, Zhuang J. Pathophysiology and therapeutic advances in myeloma bone disease. Chronic Dis Transl Med. 2022;8(4):264–270. doi: 10.1002/cdt3.35
   PubMedGoogle Scholar
• Rasch S, Lund T, Asmussen JT, et al. Multiple myeloma associated bone disease. Cancers (Basel). 2020;12(8):2113. doi: 10.3390/cancers12082113
   PubMed Web of Science ®Google Scholar
• Terpos E, Christoulas D, Gavriatopoulou M. Biology and treatment of myeloma related bone disease. Metabolism. 2018;80:80–90. doi: 10.1016/j.metabol.2017.11.012
   PubMed Web of Science ®Google Scholar
• Mukkamalla S, Malipeddi D. Myeloma bone disease: a comprehensive review. Int J Mol Sci. 2021;22(12):6208. doi: 10.3390/ijms22126208
   PubMed Web of Science ®Google Scholar
• Morris EV, Edwards CM. Morphogens and growth factor signalling in the myeloma bone-lining niche. Cell Mol Life Sci. 2021;78(9):4085–4093. doi: 10.1007/s00018-021-03767-0
   PubMed Web of Science ®Google Scholar
• Padala SA, Barsouk A, Barsouk A, et al. Epidemiology, staging, and management of multiple myeloma. Med Sci (Basel). 2021;9(1):3. doi: 10.3390/medsci9010003
   PubMedGoogle Scholar
• Lonial S, Popat R, Hulin C, et al. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022;9(11):e822–e832. doi: 10.1016/S2352-3026(22)00290-3
   PubMed Web of Science ®Google Scholar
• Bjorklund CC, Kang J, Amatangelo M, et al. Iberdomide (CC-220) is a potent cereblon E3 ligase modulator with antitumor and immunostimulatory activities in lenalidomide- and pomalidomide-resistant multiple myeloma cells with dysregulated CRBN. Leukemia. 2020;34(4):1197–1201. doi: 10.1038/s41375-019-0620-8
   PubMed Web of Science ®Google Scholar
• Richardson PG, Trudel S, Popat R, et al. Mezigdomide plus dexamethasone in relapsed and refractory multiple myeloma. N Engl J Med. 2023;389(11):1009–1022. doi: 10.1056/NEJMoa2303194
   PubMed Web of Science ®Google Scholar
• Andersen NF, Vogel U, Klausen TW, et al. Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myeloma. Int J Cancer. 2012;131(5):E636–E642. doi: 10.1002/ijc.27387
   PubMed Web of Science ®Google Scholar
• Kulig P, Milczarek S, Bakinowska E, et al. Lenalidomide in multiple myeloma: review of resistance mechanisms, current treatment strategies and future perspectives. Cancers (Basel). 2023;15(3):963. doi: 10.3390/cancers15030963
   PubMed Web of Science ®Google Scholar
• Liu S, Chen T, Wang R, et al. Exploring the effect of the “quaternary regulation” theory of “peripheral nerve-angiogenesis-osteoclast-osteogenesis” on osteoporosis based on neuropeptides. Front Endocrinol. 2022;13:908043. doi: 10.3389/fendo.2022.908043
   PubMed Web of Science ®Google Scholar
• Tuckermann J, Adams RH. The endothelium-bone axis in development, homeostasis and bone and joint disease. Nat Rev Rheumatol. 2021;17(10):608–620. doi: 10.1038/s41584-021-00682-3
   PubMed Web of Science ®Google Scholar
• Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323–328. doi: 10.1038/nature13145
   PubMed Web of Science ®Google Scholar
• Watanabe T. Realization of osteolysis, angiogenesis, immunosuppression, and drug resistance by extracellular vesicles: roles of RNAs and proteins in their cargoes and of ectonucleotidases of the immunosuppressive adenosinergic noncanonical pathway in the bone marrow niche of multiple myeloma. Cancers (Basel). 2021;13(12):2969. doi: 10.3390/cancers13122969
   PubMed Web of Science ®Google Scholar
• Palta A, Kaur M, Tahlan A, et al. Evaluation of angiogenesis in multiple myeloma by VEGF immunoexpression and microvessel density. J Lab Physicians. 2020;12(1):38–43. doi: 10.1055/s-0040-1714933
   PubMedGoogle Scholar
• Tanaka Y, Abe M, Hiasa M, et al. Myeloma cell-osteoclast interaction enhances angiogenesis together with bone resorption: a role for vascular endothelial cell growth factor and osteopontin. Clin Cancer Res. 2007;13(3):816–823. doi: 10.1158/1078-0432.CCR-06-2258
   PubMed Web of Science ®Google Scholar
• Soysa NS, Alles N. Positive and negative regulators of osteoclast apoptosis. Bone Rep. 2019;11:100225. doi: 10.1016/j.bonr.2019.100225
   PubMedGoogle Scholar
• Gau YC, Yeh TJ, Hsu CM, et al. Pathogenesis and treatment of myeloma-related bone disease. Int J Mol Sci. 2022;23(6):3112. doi: 10.3390/ijms23063112
   PubMed Web of Science ®Google Scholar
• Udagawa N, Koide M, Nakamura M, et al. Osteoclast differentiation by RANKL and OPG signaling pathways. J Bone Miner Metab. 2021;39(1):19–26. doi: 10.1007/s00774-020-01162-6
   PubMed Web of Science ®Google Scholar
• Deligiorgi MV, Panayiotidis MI, Griniatsos J, et al. Harnessing the versatile role of OPG in bone oncology: counterbalancing RANKL and TRAIL signaling and beyond. Clin Exp Metastasis. 2020;37(1):13–30. doi: 10.1007/s10585-019-09997-8
   PubMed Web of Science ®Google Scholar
• Terpos E, Efstathiou E, Christoulas D, et al. RANKL inhibition: clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases. Expert Opin Biol Ther. 2009;9(4):465–479. doi: 10.1517/14712590902845610
   PubMed Web of Science ®Google Scholar
• Xu Y, Hu J, Lv Q, et al. Endometrium-derived mesenchymal stem cells suppress progression of endometrial cancer via the DKK1-wnt/beta-catenin signaling pathway. Stem Cell Res Ther. 2023;14(1):159. doi: 10.1186/s13287-023-03387-4
   PubMed Web of Science ®Google Scholar
• Kuljanin M, Bell GI, Sherman SE, et al. Proteomic characterisation reveals active wnt-signalling by human multipotent stromal cells as a key regulator of beta cell survival and proliferation. Diabetologia. 2017;60(10):1987–1998. doi: 10.1007/s00125-017-4355-7
   PubMed Web of Science ®Google Scholar
• Nierste BA, Glackin CA, Kirshner J. Dkk-1 and IL-7 in plasma of patients with multiple myeloma prevent differentiation of mesenchymal stem cells into osteoblasts. Am J Blood Res. 2014;4(2):73–85.
   PubMedGoogle Scholar
• Terpos E, Ntanasis-Stathopoulos I, Dimopoulos MA. Myeloma bone disease: from biology findings to treatment approaches. Blood. 2019;133(14):1534–1539. doi: 10.1182/blood-2018-11-852459
   PubMed Web of Science ®Google Scholar
• Zhang F, Zhang Z, Sun D, et al. EphB4 promotes osteogenesis of CTLA4-modified bone marrow-derived mesenchymal stem cells through cross talk with wnt pathway in xenotransplantation. Tissue Eng Part A. 2015;21(17–18):2404–2416. doi: 10.1089/ten.tea.2015.0012
   PubMed Web of Science ®Google Scholar
• Atsuta I, Liu S, Miura Y, et al. Mesenchymal stem cells inhibit multiple myeloma cells via the fas/fas ligand pathway. Stem Cell Res Ther. 2013;4(5):111. doi: 10.1186/scrt322
   PubMedGoogle Scholar
• Akhmetzyanova I, Aaron T, Galbo P, et al. Tissue-resident macrophages promote early dissemination of multiple myeloma via IL-6 and TNFalpha. Blood Adv. 2021;5(18):3592–3608. doi: 10.1182/bloodadvances.2021005327
   PubMed Web of Science ®Google Scholar
• Tai YT, Cho SF, Anderson KC. Osteoclast immunosuppressive effects in multiple myeloma: role of programmed cell death ligand 1. Front Immunol. 2018;9:1822. doi: 10.3389/fimmu.2018.01822
   PubMed Web of Science ®Google Scholar
• Zhang XX, Zhang LF, Liu L, et al. Effect of bone marrow mesenchymal stem cells in patients with multiple myeloma on migration of myeloma cells in vitro. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018;26(2):484–488. doi: 10.7534/j.issn.1009-2137.2018.02.030
   PubMedGoogle Scholar
• Bouyssou JM, Ghobrial IM, Roccaro AM. Targeting SDF-1 in multiple myeloma tumor microenvironment. Cancer Lett. 2016;380(1):315–318. doi: 10.1016/j.canlet.2015.11.028
   PubMed Web of Science ®Google Scholar
• Gupta D, Treon SP, Shima Y, et al. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia. 2001;15(12):1950–1961. doi: 10.1038/sj.leu.2402295
   PubMed Web of Science ®Google Scholar
• Zhu YX, Kortuem KM, Stewart AK. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013;54(4):683–687. doi: 10.3109/10428194.2012.728597
   PubMed Web of Science ®Google Scholar
• Krejcik J, Barnkob MB, Nyvold CG, et al. Harnessing the immune system to fight multiple myeloma. Cancers (Basel). 2021;13(18):4546. doi: 10.3390/cancers13184546
   PubMed Web of Science ®Google Scholar
• Ria R, Vacca A. Bone marrow stromal cells-induced drug resistance in multiple myeloma. Int J Mol Sci. 2020;21(2):613. doi: 10.3390/ijms21020613
   PubMed Web of Science ®Google Scholar
• Fernandez-Lazaro D, Fernandez-Lazaro CI, Caballero GA, et al. Immunomodulator drugs for the treatment of multiple myeloma. Rev Med Chil. 2018;146(12):1444–1451. doi: 10.4067/s0034-98872018001201444
   PubMed Web of Science ®Google Scholar
• Yasui K, Yashiro M, Tsuge M, et al. Thalidomide dramatically improves the symptoms of early-onset sarcoidosis/blau syndrome: its possible action and mechanism. Arthritis Rheum. 2010;62(1):250–257. doi: 10.1002/art.25035
   PubMed Web of Science ®Google Scholar
• Mercurio A, Adriani G, Catalano A, et al. A mini-review on thalidomide: chemistry, mechanisms of action, therapeutic potential and anti-angiogenic properties in multiple myeloma. Curr Med Chem. 2017;24(25):2736–2744. doi: 10.2174/0929867324666170601074646
   PubMed Web of Science ®Google Scholar
• Breitkreutz I, Vallet S, Raab MS, et al. Lenalidomide and bortezomib inhibit osteoclast differentiation and activation in multiple myeloma: clinical implications. Blood. 2006;108(11):3485. doi: 10.1182/blood.V108.11.3485.3485
   Web of Science ®Google Scholar
• Qu X, Mei J, Yu Z, et al. Lenalidomide regulates osteocytes fate and related osteoclastogenesis via IL-1beta/NF-kappaB/RANKL signaling. Biochem Biophys Res Commun. 2018;501(2):547–555. doi: 10.1016/j.bbrc.2018.05.035
   PubMed Web of Science ®Google Scholar
• Bolzoni M, Storti P, Bonomini S, et al. Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules. Exp Hematol. 2013;41(4):387–97.e1. doi: 10.1016/j.exphem.2012.11.005
   PubMed Web of Science ®Google Scholar
• Holstein SA, Suman VJ, McCarthy PL. Update on the role of lenalidomide in patients with multiple myeloma. Ther Adv Hematol. 2018;9(7):175–190. doi: 10.1177/2040620718775629
   PubMed Web of Science ®Google Scholar
• Heider U, Kaiser M, Muller C, et al. Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment. Eur J Haematol. 2006;77(3):233–238. doi: 10.1111/j.1600-0609.2006.00692.x
   PubMed Web of Science ®Google Scholar
• Bolomsky A, Schreder M, Meissner T, et al. Immunomodulatory drugs thalidomide and lenalidomide affect osteoblast differentiation of human bone marrow stromal cells in vitro. Exp Hematol. 2014;42(7):516–525. doi: 10.1016/j.exphem.2014.03.005
   PubMed Web of Science ®Google Scholar
• Knobloch J, Shaughnessy JJ, Ruther U. Thalidomide induces limb deformities by perturbing the bmp/Dkk1/Wnt signaling pathway. FASEB J. 2007;21(7):1410–1421. doi: 10.1096/fj.06-7603com
   PubMed Web of Science ®Google Scholar
• Munemasa S, Sakai A, Kuroda Y, et al. Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation. Int J Oncol. 2008;33(1):129–36. doi: 10.3892/ijo.33.1.129
   PubMed Web of Science ®Google Scholar
• Ganesan S, Palani HK, Balasundaram N, et al. Combination lenalidomide/bortezomib treatment synergistically induces calpain-dependent ikaros cleavage and apoptosis in myeloma cells. Mol Cancer Res. 2020;18(4):529–536. doi: 10.1158/1541-7786.MCR-19-0431
   PubMed Web of Science ®Google Scholar
• Son E, Do H, Joo HM, et al. Induction of alkaline phosphatase activity by L-ascorbic acid in human osteoblastic cells: a potential role for CK2 and Ikaros. Nutrition. 2007;23(10):745–753. doi: 10.1016/j.nut.2007.06.013
   PubMed Web of Science ®Google Scholar
• Tosi P, Zamagni E, Cellini C, et al. First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma. Eur J Haematol. 2006;76(5):399–404. doi: 10.1111/j.0902-4441.2005.t01-1-EJH2520.x
   PubMed Web of Science ®Google Scholar
• Terpos E, Mihou D, Szydlo R, et al. The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRankl/osteoprotegerin ratio. Leukemia. 2005;19(11):1969–1976. doi: 10.1038/sj.leu.2403890
   PubMed Web of Science ®Google Scholar
• Bao L, Lu XJ, Zhang XH, et al. Effect of different regimens on bone disease of multiple myeloma. Zhonghua Xue Ye Xue Za Zhi. 2011;32(4):221–225.
   PubMedGoogle Scholar
• Terpos E, Christoulas D, Kastritis E, et al. VTD consolidation, without bisphosphonates, reduces bone resorption and is associated with a very low incidence of skeletal-related events in myeloma patients post ASCT. Leukemia. 2014;28(4):928–934. doi: 10.1038/leu.2013.267
   PubMed Web of Science ®Google Scholar
• Terpos E, Kastritis E, Roussou M, et al. The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia. 2008;22(12):2247–2256. doi: 10.1038/leu.2008.235
   PubMed Web of Science ®Google Scholar
• Gavriatopoulou M, Terpos E, Ntanasis-Stathopoulos I, et al. Consolidation with carfilzomib, lenalidomide, and dexamethasone (KRd) following ASCT results in high rates of minimal residual disease negativity and improves bone metabolism, in the absence of bisphosphonates, among newly diagnosed patients with multiple myeloma. Blood Cancer J. 2020;10(3):25.
   PubMed Web of Science ®Google Scholar
• Terpos E, Ntanasis-Stathopoulos I, Katodritou E, et al. Carfilzomib improves bone metabolism in patients with advanced relapsed/refractory multiple myeloma: results of the CarMMa study. Cancers (Basel). 2021;13(6):1257. doi: 10.3390/cancers13061257
   PubMed Web of Science ®Google Scholar
• Terpos E, Christoulas D, Kastritis E, et al. The combination of lenalidomide and dexamethasone reduces bone resorption in responding patients with relapsed/refractory multiple myeloma but has no effect on bone formation: final results on 205 patients of the Greek myeloma study group. Am J Hematol. 2014;89(1):34–40. doi: 10.1002/ajh.23577
   PubMed Web of Science ®Google Scholar
• Terpos E, Katodritou E, Symeonidis A, et al. Effect of induction therapy with lenalidomide, doxorubicin and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma. Int J Cancer. 2019;145(2):559–568. doi: 10.1002/ijc.32125
   PubMed Web of Science ®Google Scholar
• Terpos E, Kastritis E, Ntanasis-Stathopoulos I, et al. Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: effects on survival and bone outcomes in the absence of bisphosphonates. Am J Hematol. 2019;94(4):400–407. doi: 10.1002/ajh.25392
   PubMed Web of Science ®Google Scholar
• Breitkreutz I, Raab MS, Vallet S, et al. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia. 2008;22(10):1925–1932. doi: 10.1038/leu.2008.174
   PubMed Web of Science ®Google Scholar
• Morgan GJ, Davies FE, Gregory WM, et al. Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the medical research council myeloma IX trial. Blood. 2012;119(23):5374–5383. doi: 10.1182/blood-2011-11-392522
   PubMed Web of Science ®Google Scholar
• Olszewski AJ, Barth PM, Reagan JL. Use of bone-modifying agents and clinical outcomes in older adults with multiple myeloma. Cancer Med. 2019;8(16):6945–6954. doi: 10.1002/cam4.2591
   PubMed Web of Science ®Google Scholar
• Bahlis NJ, Siegel DS, Schiller GJ, et al. Pomalidomide, dexamethasone, and daratumumab immediately after lenalidomide-based treatment in patients with multiple myeloma: updated efficacy, safety, and health-related quality of life results from the phase 2 MM-014 trial. Leuk Lymphoma. 2022;63(6):1407–1417. doi: 10.1080/10428194.2022.2030477
   PubMed Web of Science ®Google Scholar
• Soekojo CY, Kim K, Huang SY, et al. Pomalidomide and dexamethasone combination with additional cyclophosphamide in relapsed/refractory multiple myeloma (AMN001)-a trial by the Asian myeloma network. Blood Cancer J. 2019;9(10):83. doi: 10.1038/s41408-019-0245-1
   PubMedGoogle Scholar
• Dimopoulos MA, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6):801–812. doi: 10.1016/S1470-2045(21)00128-5
   PubMed Web of Science ®Google Scholar