Advertisement

Multiple Myeloma in Older Adults

  • Ashley RoskoEmail author
  • Geetika Bhatt
  • Eben Lichtman
  • Sascha Tuchman
Living reference work entry

Abstract

Multiple myeloma (MM) is a plasma cell malignancy of older adults and incidence is expected to increase in the coming years. Despite substantial improvements in patient survival, the disease remains incurable. Early mortality is most common in adults 70 years and older. Novel therapeutics and autologous stem cell transplant (ASCT) have led to improvement in survival; however, transplant eligibility remains a challenge especially in the older adult population. Understanding geriatric assessment evaluations can aid in identifying patients at risk for increased morbidity and mortality in older adults with MM. Novel treatment combinations have improved disease control while balancing efficacy with toxicity for the older adult. Here we explore the diagnostic criteria, staging systems, cytogenetic abnormalities, treatment approach, and geriatric assessment in older adults with MM.

Keywords

Multiple myeloma Autologous stem cell transplant Geriatric assessment 

References

  1. Alexanian R, Haut A, Khan AU, Lane M, McKelvey EM, Migliore PJ, et al. Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens. JAMA. 1969;208(9):1680–5.PubMedCrossRefGoogle Scholar
  2. Al-Hamadani M, Hashmi SK, Go RS. Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio-geo-demographic factors in the era of novel agents. Am J Hematol. 2014;89(8):825–30.PubMedCrossRefGoogle Scholar
  3. Anagnostopoulos A, Gika D, Symeonidis A, Zervas K, Pouli A, Repoussis P, et al. Multiple myeloma in elderly patients: prognostic factors and outcome. Eur J Haematol. 2005;75(5):370–5.PubMedCrossRefGoogle Scholar
  4. Anderson KC, Alsina M, Atanackovic D, Biermann JS, Chandler JC, Costello C, et al. Multiple myeloma, version 2.2016: clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2015;13(11):1398–435.CrossRefGoogle Scholar
  5. Annesley TM, Burritt MF, Kyle RA. Artifactual hypercalcemia in multiple myeloma. Mayo Clin Proc. 1982;57(9):572–5.PubMedGoogle Scholar
  6. Attal M, Blaise D, Marit G, Payen C, Michallet M, Vernant JP, et al. Consolidation treatment of adult acute lymphoblastic-leukemia – a prospective, randomized trial comparing allogeneic versus autologous bone-marrow transplantation and testing the impact of recombinant interleukin-2 after autologous bone-marrow transplantation. Blood. 1995;86(4):1619–28.PubMedGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. Attal M, Lauwers-Cances V, Hulin C, Facon T, Caillot D, Escoffre M, et al. Autologous transplantation for multiple myeloma in the era of new drugs: a phase III study of the Intergroupe Francophone Du Myelome (IFM/DFCI 2009 trial). Blood. 2015;126(23):391.Google Scholar
  9. Auner HW, Garderet L, Kroger N. Autologous haematopoietic cell transplantation in elderly patients with multiple myeloma. Br J Haematol. 2015b;171(4):453–62.PubMedCrossRefGoogle Scholar
  10. Auner HW, Szydlo R, Hoek J, Goldschmidt H, Stoppa AM, Morgan GJ, et al. Trends in autologous hematopoietic cell transplantation for multiple myeloma in Europe: increased use and improved outcomes in elderly patients in recent years. Bone Marrow Transplant. 2015a;50(2):209–15.PubMedCrossRefGoogle Scholar
  11. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood. 2007;109(8):3489–95.PubMedCrossRefGoogle Scholar
  12. Avet-Loiseau H, Durie BG, Cavo M, Attal M, Gutierrez N, Haessler J, et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia. 2013;27(3):711–7.PubMedCrossRefGoogle Scholar
  13. Bashir Q, Shah N, Parmar S, Wei W, Rondon G, Weber DM, et al. Feasibility of autologous hematopoietic stem cell transplant in patients aged >/=70 years with multiple myeloma. Leuk Lymphoma. 2012;53(1):118–22.PubMedCrossRefGoogle Scholar
  14. Bataille R, Durie BG, Grenier J. Serum beta2 microglobulin and survival duration in multiple myeloma: a simple reliable marker for staging. Br J Haematol. 1983;55(3):439–47.PubMedCrossRefGoogle Scholar
  15. Bataille R, Durie BG, Grenier J, Sany J. Prognostic factors and staging in multiple myeloma: a reappraisal. J Clin Oncol. 1986;4(1):80–7.PubMedCrossRefGoogle Scholar
  16. Baz R, Alemany C, Green R, Hussein MA. Prevalence of vitamin B12 deficiency in patients with plasma cell dyscrasias: a retrospective review. Cancer. 2004;101(4):790–5.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. Boyd KD, Ross FM, Chiecchio L, Dagrada GP, Konn ZJ, Tapper WJ, et al. A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial. Leukemia. 2012;26(2):349–55.PubMedCrossRefGoogle Scholar
  19. Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010;116(23):4745–53.PubMedCrossRefGoogle Scholar
  20. Buckman R, Cuzick J, Galton DA. Long-term survival in myelomatosis. A report to the MRC working party on leukaemia in adults. Br J Haematol. 1982;52(4):589–99.PubMedCrossRefGoogle Scholar
  21. Carbone PP, Kellerhouse LE, Gehan EA. Plasmacytic myeloma. A study of the relationship of survival to various clinical manifestations and anomalous protein type in 112 patients. Am J Med. 1967;42(6):937–48.PubMedCrossRefGoogle Scholar
  22. Cassuto JP, Krebs BP, Viot G, Dujardin P, Masseyeff R. Beta 2 microglobulin, a tumour marker of lymphoproliferative disorders. Lancet. 1978;2(8080):108–9.PubMedCrossRefGoogle Scholar
  23. Cavo M, Beksac M, Dimopoulos M, Pantani L, Gay F, Hájek R, et al. Intensification therapy with Bortezomib-Melphalan-prednisone versus autologous stem cell transplantation for newly diagnosed multiple myeloma: an intergroup, multicenter, phase III study of the European Myeloma Network (EMN02/HO95 MM trial). Blood. 2016b;128(22):673.Google Scholar
  24. Cavo M, Palumbo A, Zweegman S, et al. Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): a randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial). Abstract #8000. Presented at the 2016 American Society of Clinical Oncology Annual Meeting, Chicago, June 3, 2016a.Google Scholar
  25. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010;376(9758):2075–85.PubMedCrossRefGoogle Scholar
  26. Cavo M, Terpos E, Nanni C, Moreau P, Lentzsch S, Zweegman S, et al. Role of (18)F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group. Lancet Oncol. 2017;18(4):e206–e17.PubMedCrossRefGoogle Scholar
  27. De Bergsagel DE, Migliore PJ, Griffith KM. Myeloma proteins and the clinical response to melphalan therapy. Science. 1965;148(3668):376–7.CrossRefGoogle Scholar
  28. Dimopoulos MA, Barlogie B, Smith TL, Alexanian R. High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma. Ann Intern Med. 1991;115(12):931–5.PubMedCrossRefGoogle Scholar
  29. Dimopoulos MA, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010;28(33):4976–84.PubMedCrossRefGoogle Scholar
  30. Dispenzieri A, Rajkumar SV, Gertz MA, Fonseca R, Lacy MQ, Bergsagel PL, et al. Treatment of newly diagnosed multiple myeloma based on Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART): consensus statement. Mayo Clin Proc. 2007;82(3):323–41.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. Durie BGM, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet, 2017;389(10068): 519–527.CrossRefGoogle Scholar
  33. Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M, et al. Myeloma management guidelines: a consensus report from the scientific advisors of the International Myeloma Foundation. Hematol J. 2003;4(6):379–98.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. Durie BG, Stock-Novack D, Salmon SE, Finley P, Beckord J, Crowley J, et al. Prognostic value of pretreatment serum beta 2 microglobulin in myeloma: a Southwest Oncology Group Study. Blood. 1990;75(4):823–30.PubMedGoogle Scholar
  36. Engelhardt M, Dold SM, Ihorst G, Zober A, Moller M, Reinhardt H, et al. Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores. Haematologica. 2016;101(9):1110–9.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99?06): a randomised trial. Lancet. 2007a;370(9594):1209–18.PubMedCrossRefGoogle Scholar
  38. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007b;370(9594):1209–18.PubMedCrossRefGoogle Scholar
  39. Ferrucci L, Balducci L. Anemia of aging: the role of chronic inflammation and cancer. Semin Hematol. 2008;45(4):242–9.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M, et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004;64(4):1546–58.PubMedCrossRefGoogle Scholar
  41. Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23(12):2210–21.PubMedPubMedCentralCrossRefGoogle Scholar
  42. Garderet L, Beohou E, Caillot D, Stoppa AM, Touzeau C, Chretien ML, et al. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study. Haematologica. 2016;101(11):1390–7.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S, Leung N, et al. Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant. 2007;39(10):605–11.PubMedCrossRefGoogle Scholar
  45. Gleeson TG, Moriarty J, Shortt CP, Gleeson JP, Fitzpatrick P, Byrne B, et al. Accuracy of whole-body low-dose multidetector CT (WBLDCT) versus skeletal survey in the detection of myelomatous lesions, and correlation of disease distribution with whole-body MRI (WBMRI). Skelet Radiol. 2009;38(3):225–36.CrossRefGoogle Scholar
  46. Greenberg AJ, Rajkumar SV, Vachon CM. Familial monoclonal gammopathy of undetermined significance and multiple myeloma: epidemiology, risk factors, and biological characteristics. Blood. 2012;119(23):5359–66.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. Guralnik JM, Ershler WB, Schrier SL, Picozzi VJ. Anemia in the elderly: a public health crisis in hematology. Hematology Am Soc Hematol Educ Program. 2005;2005:528–32.CrossRefGoogle Scholar
  49. Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy – a systematic review. Leuk Res. 2014;38(3):275–83.PubMedCrossRefGoogle Scholar
  50. Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(30):4621–9.CrossRefGoogle Scholar
  51. Huang LW, Bacon W, Cirrincione C, Peterson B, Long G, Rizzieri D, et al. Efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma. Hematol Oncol. 2017;35(4):752–9.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Jacobson JL, Hussein MA, Barlogie B, Durie BG, Crowley JJ, Southwest Oncology G. A new staging system for multiple myeloma patients based on the Southwest Oncology Group (SWOG) experience. Br J Haematol. 2003;122(3):441–50.PubMedCrossRefGoogle Scholar
  53. Jaglowski SM, Ruppert AS, Hofmeister CC, Elder P, Blum W, Klisovic R, et al. The hematopoietic stem cell transplant comorbidity index can predict for 30-day readmission following autologous stem cell transplant for lymphoma and multiple myeloma. Bone Marrow Transplant. 2014;49(10):1323–9.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Jimenez-Zepeda, V.H., et al. Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible Multiple Myeloma. Blood. 2015;126(23).Google Scholar
  55. Kastritis E, Zagouri F, Symeonidis A, Roussou M, Sioni A, Pouli A, et al. Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma. Leukemia. 2014;28(10):2075–9.PubMedCrossRefGoogle Scholar
  56. Kooman JP. Estimation of renal function in patients with chronic kidney disease. J Magn Reson Imaging. 2009;30(6):1341–6.PubMedCrossRefGoogle Scholar
  57. Kumar S, Flinn IW, Richardson PG, Hari P, Callander NS, Noga SJ, et al. Novel three- and four-drug combination regimens of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide, for previously untreated multiple myeloma: results from the multi-center, randomized, phase 2 EVOLUTION study. Blood. 2010;116(21):273.Google Scholar
  58. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328–46.PubMedCrossRefGoogle Scholar
  59. Kumar SK, Dingli D, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, et al. Autologous stem cell transplantation in patients of 70 years and older with multiple myeloma: results from a matched pair analysis. Am J Hematol. 2008;83(8):614–7.PubMedCrossRefGoogle Scholar
  60. 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.PubMedCrossRefGoogle Scholar
  61. Kumar SK, Mikhael JR, Buadi FK, Dingli D, Dispenzieri A, Fonseca R, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines. Mayo Clin Proc. 2009;84(12):1095–110.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Kusumoto S, Jinnai I, Itoh K, Kawai N, Sakata T, Matsuda A, et al. Magnetic resonance imaging patterns in patients with multiple myeloma. Br J Haematol. 1997;99(3):649–55.PubMedCrossRefGoogle Scholar
  63. Kyle RA. Multiple myeloma: an odyssey of discovery. Br J Haematol. 2000;111(4):1035–44.PubMedCrossRefGoogle Scholar
  64. 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.PubMedCrossRefGoogle Scholar
  65. Leung N, Gertz MA, Zeldenrust SR, Rajkumar SV, Dispenzieri A, Fervenza FC, et al. Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains. Kidney Int. 2008;73(11):1282–8.PubMedCrossRefGoogle Scholar
  66. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67(6):2089–100.PubMedCrossRefGoogle Scholar
  67. Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373(7):621–31.PubMedCrossRefGoogle Scholar
  68. Mateos MV, Oriol A, Martinez-Lopez J, Gutierrez N, Teruel AI, de Paz R, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol. 2010b;11(10):934–41.PubMedCrossRefGoogle Scholar
  69. Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010a;28(13):2259–66.PubMedCrossRefGoogle Scholar
  70. Mateos MV, Richardson PG, Shi HL, Niculescu L, Elliott J, Dow E, et al. Higher cumulative bortezomib dose results in better overall survival (OS) in patients with previously untreated multiple myeloma (MM) receiving bortezomib-melphalan-prednisone (VMP) in the phase 3 VISTA study. Blood. 2013;122(21):1968.Google Scholar
  71. Mateos MV, San Miguel JF. How should we treat newly diagnosed multiple myeloma patients? Hematology Am Soc Hematol Educ Program. 2013;2013:488–95.PubMedCrossRefGoogle Scholar
  72. Merlini G, Waldenstrom JG, Jayakar SD. A new improved clinical staging system for multiple myeloma based on analysis of 123 treated patients. Blood. 1980;55(6):1011–9.PubMedGoogle Scholar
  73. Merz M, Neben K, Raab MS, Sauer S, Egerer G, Hundemer M, et al. Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents. Ann Oncol. 2014;25(1):189–95.PubMedCrossRefGoogle Scholar
  74. Neben K, Jauch A, Bertsch U, Heiss C, Hielscher T, Seckinger A, et al. Combining information regarding chromosomal aberrations t(4;14) and del(17p13) with the international staging system classification allows stratification of myeloma patients undergoing autologous stem cell transplantation. Haematologica. 2010;95(7):1150–7.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, et al. Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol. 2015;33(33):3921–9.PubMedCrossRefGoogle Scholar
  76. Norfolk D, Child JA, Cooper EH, Kerruish S, Ward AM. Serum beta 2-microglobulin in myelomatosis: potential value in stratification and monitoring. Br J Cancer. 1980;42(4):510–5.PubMedPubMedCentralCrossRefGoogle Scholar
  77. O’Donnell ELJ, Yee AJ, Huff CA, Basile F, Wade FM, Paba-Prada CE, Ghobrial IM, Schlossman RL, Couture N, Doherty L, Lyons H, English C, Munshi N, Anderson KC, Richardson PG, Raje N. A phase II study of modified lenalidomide, bortezomib, and dexamethasone (RVD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. Orlando: American Society of Hematology; 2015. Blood 2015Google Scholar
  78. Pal SK, Katheria V, Hurria A. Evaluating the older patient with cancer: understanding frailty and the geriatric assessment. CA Cancer J Clin. 2010;60(2):120–32.PubMedCrossRefGoogle Scholar
  79. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol. 2015a;33(26):2863–9.PubMedPubMedCentralCrossRefGoogle Scholar
  80. Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367(9513):825–31.PubMedCrossRefGoogle Scholar
  81. Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015b;125(13):2068–74.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905.CrossRefGoogle Scholar
  83. Palumbo A, Waage A, Hulin C, Beksac M, Zweegman S, Gay F, et al. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials. Haematologica. 2013;98(1):87–94.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Prognostic features in the third MRC myelomatosis trial. Medical Research Council’s working party on Leukaemia in adults. Br J Cancer. 1980;42(6):831–40.CrossRefGoogle Scholar
  85. 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.PubMedCrossRefGoogle Scholar
  86. Rajkumar SV, Jacobus S, Callander NS. 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. (vol 11, pg 29, 2010). Lancet Oncol. 2010;11(1):14.CrossRefGoogle Scholar
  87. Regelink JC, Minnema MC, Terpos E, Kamphuis MH, Raijmakers PG, Pieters-van den Bos IC, et al. Comparison of modern and conventional imaging techniques in establishing multiple myeloma-related bone disease: a systematic review. Br J Haematol. 2013;162(1):50–61.PubMedCrossRefGoogle Scholar
  88. Report on the first myelomatosis trial. I. Analysis of presenting features of prognostic importance. Br J Haematol. 1973;24(1):123–39.CrossRefGoogle Scholar
  89. Richardson DR, et al. Psychosocial risk predicts high readmission rates for hematopoietic cell transplant recipients. Bone Marrow Transplantation. 2018;53(11):1418–1427.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Rodin MB, Mohile SG. A practical approach to geriatric assessment in oncology. J Clin Oncol. 2007;25(14):1936–44.PubMedCrossRefGoogle Scholar
  91. Rosko A, Artz A. Aging: treating the older patient. Biol Blood Marrow Transplant. 2017;23(2):193–200.PubMedCrossRefGoogle Scholar
  92. Rosko, A.E., et al. Use of a comprehensive frailty assessment to predict morbidity in patients with multiple myeloma undergoing transplant. J Geriatr Oncol. 2018.Google Scholar
  93. Rustizky V. Multiples Myelom. Deutsche Zeitschrift für Chirurgie. 1873;3(1):162–72.CrossRefGoogle Scholar
  94. Saad A, Mahindra A, Zhang MJ, Zhong X, Costa LJ, Dispenzieri A, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2014b;20(3):402–8e1.PubMedCrossRefGoogle Scholar
  95. Saad A, Mahindra A, Zhang MJ, Zhong XB, Costa LJ, Dispenzieri A, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2014a;20(3):402–8.PubMedCrossRefGoogle Scholar
  96. Sánchez-Ortega I, et al. Autologous Hematopoietic Cell Transplantation in Elderly Patients Aged 65 and Older: A Retrospective Analysis By the Complications and Quality of Life Working Party of the EBMT. Blood, 2016;128(22).Google Scholar
  97. Sharma M, Zhang MJ, Zhong X, Abidi MH, Akpek G, Bacher U, et al. Older patients with myeloma derive similar benefit from autologous transplantation. Biol Blood Marrow Transplant. 2014;20(11):1796–803.PubMedPubMedCentralCrossRefGoogle Scholar
  98. Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N, et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood. 1999;93(1):51–4.PubMedGoogle Scholar
  99. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. Ca-Cancer J Clin. 2016;66(1):7–30.PubMedCrossRefGoogle Scholar
  100. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758–65.PubMedCrossRefGoogle Scholar
  101. Sorror ML, Giralt S, Sandmaier BM, De Lima M, Shahjahan M, Maloney DG, et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood. 2007;110(13):4606–13.PubMedPubMedCentralCrossRefGoogle Scholar
  102. Surveillance Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database. 2017.
  103. Terpos E, Katodritou E, Roussou M, Pouli A, Michalis E, Delimpasi S, et al. High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents. Eur J Haematol. 2010;85(2):114–9.PubMedGoogle Scholar
  104. Warren JL, Harlan LC, Stevens J, Little RF, Abel GA. Multiple myeloma treatment transformed: a population-based study of changes in initial management approaches in the United States. J Clin Oncol. 2013;31(16):1984–9.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Weinstein JR, Anderson S. The aging kidney: physiological changes. Adv Chronic Kidney Dis. 2010;17(4):302–7.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Wildes TM, Finney JD, Fiala M, Gao F, Vij R, Stockerl-Goldstein K, et al. High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma. Bone Marrow Transplant. 2015a;50(8):1075–82.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Wildes TM, Finney JD, Fiala M, Gao F, Vij R, Stockerl-Goldstein K, et al. High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma. Bone Marrow Transplant. 2015b;50(8):1075–82.PubMedPubMedCentralCrossRefGoogle Scholar
  108. Wong KY, Li Z, Zhang X, Leung GK, Chan GC, Chim CS. Epigenetic silencing of a long non-coding RNA KIAA0495 in multiple myeloma. Mol Cancer. 2015;14:175.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Wright JH. A case of multiple myeloma. Trans Assoc Am Phys. 1900a;15:137–47.Google Scholar
  110. Wright JH. A case of multiple myeloma. Johns Hopkins Hospital Rep. 1900b;9:359–66.Google Scholar
  111. Zweegman S, van der Holt B, Mellqvist UH, Salomo M, Bos GM, Levin MD, et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016;127(9):1109–16.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ashley Rosko
    • 1
    Email author
  • Geetika Bhatt
    • 2
  • Eben Lichtman
    • 3
  • Sascha Tuchman
    • 3
  1. 1.Division of HematologyThe Ohio State UniversityColumbusUSA
  2. 2.University Hospitals Seidman Cancer CenterCase Western Reserve UniversityClevelandUSA
  3. 3.Division of Hematology and OncologyUniversity of North Carolina – Chapel Hill Comprehensive Cancer CenterChapel HillUSA

Section editors and affiliations

  • Heidi Klepin
    • 1
  1. 1.Comprehensive Cancer Center of Wake Forest UniversityWinston-SalemUSA

Personalised recommendations