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Myeloma

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Abstract

Multiple myeloma (MM) is a clonal malignant disorder of mature B-lymphocytes characterized by extensive proliferation and accumulation of aberrant plasma cells in the bone marrow. Extramedullary disease, containing clusters of malignant plasma cells, occurs in some patients and is referred to as plasmacytoma. MM is preceded by an asymptomatic premalignant disorder, monoclonal gammopathy of undetermined significance (MGUS), in almost all patients. Clinical manifestations due to disruption of normal hematopoiesis and immune dysfunction include fatigue, anemia and infections. Osteolytic bone disease is a major cause of morbidity in MM and is associated with hypercalcemia, osteopenia, and pathologic fractures. Monoclonal immunoglobulin or M-protein secreted by the clonal plasma cells may lead to renal insufficiency, and peripheral neuropathy. Despite a significant in improvement of survival over the past decade with the advent of novel biologic therapeutic agents, MM is considered an incurable disease. Risk adapted therapy with incorporation of novel agents is recommended for the initial treatment of MM with consideration for autologous hematopoietic stem cell transplantation in eligible patients. In this chapter, the epidemiology, pathogenesis of bone disease in MM, diagnosis, and treatment principles of MM are discussed.

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References

  1. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351(18):1860–73. PubMed PMID: 15509819.

    Article  CAS  PubMed  Google Scholar 

  2. Rajkumar SV. Multiple myeloma: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol. 2013;88(3):226–35. PubMed PMID: 23440663.

    Article  PubMed  Google Scholar 

  3. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. Cancer J Clin. 2014;64(1):9–29. PubMed PMID: 24399786.

    Article  Google Scholar 

  4. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton 3rd LJ. Incidence of multiple myeloma in Olmsted County, Minnesota: trend over 6 decades. Cancer. 2004;101(11):2667–74. PubMed PMID: 15481060.

    Article  PubMed  Google Scholar 

  5. Turesson I, Velez R, Kristinsson SY, Landgren O. Patterns of multiple myeloma during the past 5 decades: stable incidence rates for all age groups in the population but rapidly changing age distribution in the clinic. Mayo Clin Proc. 2010;85(3):225–30. PubMed PMID: 20194150. Pubmed Central PMCID: 2843108.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78(1):21–33. PubMed PMID: 12528874.

    Article  PubMed  Google Scholar 

  7. Waxman AJ, Mink PJ, Devesa SS, Anderson WF, Weiss BM, Kristinsson SY, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood. 2010;116(25):5501–6. PubMed PMID: 20823456. Pubmed Central PMCID: 3031400.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Landgren O, Kyle RA, Hoppin JA, Beane Freeman LE, Cerhan JR, Katzmann JA, et al. Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. Blood. 2009;113(25):6386–91. PubMed PMID: 19387005. Pubmed Central PMCID: 2710931.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Morgan GJ, Johnson DC, Weinhold N, Goldschmidt H, Landgren O, Lynch HT, et al. Inherited genetic susceptibility to multiple myeloma. Leukemia. 2014;28(3):518–24. PubMed PMID: 24247655.

    Article  CAS  PubMed  Google Scholar 

  10. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412–7. PubMed PMID: 19179464. Pubmed Central PMCID: 2689042.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113(22):5418–22. PubMed PMID: 19234139. Pubmed Central PMCID: 2689043.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24(6):1121–7. PubMed PMID: 20410922.

    Article  CAS  PubMed  Google Scholar 

  13. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564–9. PubMed PMID: 11856795.

    Article  PubMed  Google Scholar 

  14. Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356(25):2582–90. PubMed PMID: 17582068.

    Article  CAS  PubMed  Google Scholar 

  15. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–48. PubMed PMID: 25439696.

    Article  PubMed  Google Scholar 

  16. Kristinsson SY, Tang M, Pfeiffer RM, Bjorkholm M, Blimark C, Mellqvist UH, et al. Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood. 2010;116(15):2651–5. PubMed PMID: 20610813. Pubmed Central PMCID: 3324256.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Melton 3rd LJ, Rajkumar SV, Khosla S, Achenbach SJ, Oberg AL, Kyle RA. Fracture risk in monoclonal gammopathy of undetermined significance. J Bone Miner Res. 2004;19(1):25–30. PubMed PMID: 14753733.

    Article  PubMed  Google Scholar 

  18. Pepe J, Petrucci MT, Nofroni I, Fassino V, Diacinti D, Romagnoli E, et al. Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance. Br J Haematol. 2006;134(5):485–90. PubMed PMID: 16848794.

    Article  PubMed  Google Scholar 

  19. Farr JN, Zhang W, Kumar SK, Jacques RM, Ng AC, McCready LK, et al. Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance. Blood. 2014;123(5):647–9. PubMed PMID: 24227822.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Ng AC, Khosla S, Charatcharoenwitthaya N, Kumar SK, Achenbach SJ, Holets MF, et al. Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1alpha levels in patients with MGUS. Blood. 2011;118(25):6529–34. PubMed PMID: 22042700. Pubmed Central PMCID: 3242716.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003;349(26):2483–94. PubMed PMID: 14695408.

    Article  CAS  PubMed  Google Scholar 

  22. Qiang YW, Chen Y, Stephens O, Brown N, Chen B, Epstein J, et al. Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood. 2008;112(1):196–207. PubMed PMID: 18305214. Pubmed Central PMCID: 2435688.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Politou M, Terpos E, Anagnostopoulos A, Szydlo R, Laffan M, Layton M, et al. Role of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol. 2004;126(5):686–9. PubMed PMID: 15327520.

    Article  CAS  PubMed  Google Scholar 

  24. Sonmez M, Akagun T, Topbas M, Cobanoglu U, Sonmez B, Yilmaz M, et al. Effect of pathologic fractures on survival in multiple myeloma patients: a case control study. J Exp Clin Cancer Res. 2008;27:11. PubMed PMID: 18577267. Pubmed Central PMCID: 2438338.

    Google Scholar 

  25. Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer. 2007;110(8):1860–7. PubMed PMID: 17763372.

    Article  PubMed  Google Scholar 

  26. Bataille R, Chappard D, Basle M. Excessive bone resorption in human plasmacytomas: direct induction by tumour cells in vivo. Brit J Haematol. 1995;90(3):721–4. PubMed PMID: 7647018.

    Google Scholar 

  27. Bataille R, Chappard D, Marcelli C, Dessauw P, Baldet P, Sany J, et al. Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma. J Clin Invest. 1991;88(1):62–6. PubMed PMID: 2056131. Pubmed Central PMCID: 296003.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Roodman GD. Pathogenesis of myeloma bone disease. Leukemia. 2009;23(3):435–41. PubMed PMID: 19039321.

    Article  CAS  PubMed  Google Scholar 

  29. Roodman GD. Biology of osteoclast activation in cancer. J Clin Oncol. 2001;19(15):3562–71. PubMed PMID: 11481364.

    CAS  PubMed  Google Scholar 

  30. Kodama H, Nose M, Niida S, Yamasaki A. Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells. J Exp Med. 1991;173(5):1291–4. PubMed PubMed Central PMCID: 2118848.

    Article  CAS  PubMed  Google Scholar 

  31. Roodman GD. Mechanisms of bone metastasis. New Engl J Med. 2004;350(16):1655–64. PubMed PMID: 15084698.

    Article  CAS  PubMed  Google Scholar 

  32. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–19. PubMed PMID: 9108485.

    Article  CAS  PubMed  Google Scholar 

  33. Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C, Lazzarino M. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: a longitudinal study on 1003 consecutive patients. Ann Oncol. 2010;21(2):325–30. PubMed PMID: 19633044.

    Article  CAS  PubMed  Google Scholar 

  34. Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood. 2001;97(9):2900–2. PubMed PMID: 11313287.

    Article  CAS  PubMed  Google Scholar 

  35. van Laar R, Flinchum R, Brown N, Ramsey J, Riccitelli S, Heuck C, et al. Translating a gene expression signature for multiple myeloma prognosis into a robust high-throughput assay for clinical use. BMC Med Genomics. 2014;7:25. PubMed PMID: 24885236. Pubmed Central PMCID: 4032347.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Dimopoulos M, Terpos E, Comenzo RL, Tosi P, Beksac M, Sezer O, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia. 2009;23(9):1545–56. PubMed PMID: 19421229.

    Article  CAS  PubMed  Google Scholar 

  37. Caers J, Withofs N, Hillengass J, Simoni P, Zamagni E, Hustinx R, et al. The role of positron emission tomography-computed tomography and magnetic resonance imaging in diagnosis and follow up of multiple myeloma. Haematologica. 2014;99(4):629–37. PubMed PMID: 24688111.

    Google Scholar 

  38. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36(3):842–54. PubMed PMID: 1182674.

    Article  CAS  PubMed  Google Scholar 

  39. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Blade J, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412–20. PubMed PMID: 15809451.

    Google Scholar 

  40. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia. 2009;23(1):3–9. Pubmed Central PMCID: 2627786.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Rajkumar SV, Gahrton G, Bergsagel PL. Approach to the treatment of multiple myeloma: a clash of philosophies. Blood. 2011;118(12):3205–11. Pubmed Central PMCID: 3179390.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88(4):360–76. PubMed PMID: 23541011.

    Article  PubMed  Google Scholar 

  43. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29–37. PubMed PMID: 19853510. Pubmed Central PMCID: 3042271.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Gay F, Hayman SR, Lacy MQ, Buadi F, Gertz MA, Kumar S, et al. Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients. Blood. 2010;115(7):1343–50. PubMed PMID: 20008302. Pubmed Central PMCID: 2826759.

    Google Scholar 

  45. Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414–23. PubMed PMID: 18094721.

    Article  CAS  PubMed  Google Scholar 

  46. Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009;23(7):1337–41. PubMed PMID: 19225538. Pubmed Central PMCID: 2711213.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116(5):679–86. PubMed PMID: 20385792. Pubmed Central PMCID: 3324254.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C, et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood. 2011;118(22):5752–8. PubMed PMID: 21849487.

    Article  CAS  PubMed  Google Scholar 

  49. Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012;119(19):4375–82. PubMed PMID: 22422823.

    Article  CAS  PubMed  Google Scholar 

  50. Barlogie B, Anaissie E, van Rhee F, Haessler J, Hollmig K, Pineda-Roman M, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Brit J Haematol. 2007;138(2):176–85. PubMed PMID: 17593024.

    Article  CAS  Google Scholar 

  51. Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksac M, et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood. 2011;118(5):1239–47. PubMed PMID: 21670471.

    Google Scholar 

  52. Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906–17. PubMed PMID: 25184863.

    Article  CAS  PubMed  Google Scholar 

  53. San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9):906–17. PubMed PMID: 18753647.

    Article  CAS  PubMed  Google Scholar 

  54. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med. 1996;335(2):91–7. PubMed PMID: 8649495.

    Article  CAS  PubMed  Google Scholar 

  55. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348(19):1875–83. PubMed PMID: 12736280.

    Article  CAS  PubMed  Google Scholar 

  56. Blade J, Vesole DH, Gertz M. High-dose therapy in multiple myeloma. Blood. 2003;102(10):3469–70. PubMed PMID: 12893762.

    Article  CAS  PubMed  Google Scholar 

  57. Palumbo A, Bringhen S, Petrucci MT, Musto P, Rossini F, Nunzi M, et al. Intermediate-dose melphalan improves survival of myeloma patients aged 50 to 70: results of a randomized controlled trial. Blood. 2004;104(10):3052–7. PubMed PMID: 15265788.

    Article  CAS  PubMed  Google Scholar 

  58. Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C, et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood. 1998;92(9):3131–6. PubMed PMID: 9787148.

    CAS  PubMed  Google Scholar 

  59. Kumar SK, Lacy MQ, Dispenzieri A, Buadi FK, Hayman SR, Dingli D, et al. Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma. Cancer. 2012;118(6):1585–92. PubMed PMID: 22009602. Pubmed Central PMCID: 3262884.

    Google Scholar 

  60. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG, et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med. 2003;349(26):2495–502. PubMed PMID: 14695409.

    Article  CAS  PubMed  Google Scholar 

  61. Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108(10):3289–94. PubMed PMID: 16873668.

    Article  CAS  PubMed  Google Scholar 

  62. Spencer A, Prince HM, Roberts AW, Prosser IW, Bradstock KF, Coyle L, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009;27(11):1788–93. PubMed PMID: 19273705.

    Article  CAS  PubMed  Google Scholar 

  63. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1782–91. PubMed PMID: 22571202.

    Article  CAS  PubMed  Google Scholar 

  64. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1770–81. PubMed PMID: 22571201. Pubmed Central PMCID: 3744390.

    Google Scholar 

  65. Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366(19):1759–69. PubMed PMID: 22571200.

    Article  CAS  PubMed  Google Scholar 

  66. Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol. 2012;30(24):2946–55. PubMed PMID: 22802322.

    Article  CAS  PubMed  Google Scholar 

  67. Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120(14):2817–25. PubMed PMID: 22833546.

    Google Scholar 

  68. Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014;123(12):1826–32. PubMed PMID: 24421329. Pubmed Central PMCID: 3962162.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014;15(11):1195–206. PubMed PMID: 25242045.

    Article  CAS  PubMed  Google Scholar 

  70. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142–52. PubMed PMID: 25482145.

    Article  PubMed  Google Scholar 

  71. Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(8):874–85. PubMed PMID: 24948586.

    Article  CAS  PubMed  Google Scholar 

  72. Turesson I, Velez R, Kristinsson SY, Landgren O. Patterns of improved survival in patients with multiple myeloma in the twenty-first century: a population-based study. J Clin Oncol. 2010;28(5):830–4. PubMed PMID: 20038719. Pubmed Central PMCID: 2834396.

    Google Scholar 

  73. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122–8. PubMed PMID: 24157580. Pubmed Central PMCID: 4000285.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. International Myeloma Working G. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003;121(5):749–57. PubMed PMID: 12780789.

    Article  Google Scholar 

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  1. Division of Hematology and Hematological Malignancies, Department of Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Srinivas K. Tantravahi MBBS, MRCP & Tibor Kovacsovics MD

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  1. Srinivas K. Tantravahi MBBS, MRCP
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    R. Lor Randall

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Tantravahi, S.K., Kovacsovics, T. (2016). Myeloma. In: Randall, R. (eds) Metastatic Bone Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5662-9_9

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