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Smoldering Multiple Myeloma

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Neoplastic Diseases of the Blood

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Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10–60% bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to active MM is not uniform, and several markers are useful for identifying patients at high risk of progression. The definition of the disease has recently been revisited and asymptomatic MMs at 80–90% of progression risk at 2 years are now considered to be active MM candidates for treatment. In the future, more precise biomarkers are necessary for accurate risk stratification in order to plan an optimized follow-up according to the risk of progression, as well as to expand the group of patients that can obtain a benefit if they receive early treatment. A phase 3, randomized trial in high-risk SMM patients comparing early treatment versus observation has shown a significant benefit in terms of time to progression and overall survival for early intervention and confirmatory clinical trials will definitively contribute to establish the early treatment as standard of care in high-risk SMM.

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References

  1. Kyle RA, Greipp PR. Smoldering multiple myeloma. N Engl J Med. 1980;302(24):1347–9.

    Article  CAS  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. Kristinsson SY, Holmberg E, Blimark C. Treatment for high-risk smoldering myeloma. N Engl J Med. 2013;369(18):1762–3.

    Article  CAS  PubMed  Google Scholar 

  4. Blade J, Dimopoulos M, Rosinol L, Rajkumar SV, Kyle RA. Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J Clin Oncol. 2010;28(4):690–7.

    Article  CAS  PubMed  Google Scholar 

  5. Hillengass J, Fechtner K, Weber MA, Bauerle T, Ayyaz S, Heiss C, et al. Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol. 2010;28(9):1606–10.

    Article  PubMed  Google Scholar 

  6. Kastritis E, Moulopoulos LA, Terpos E, Koutoulidis V, Dimopoulos MA. The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma. Leukemia. 2014;28(12):2402–3.

    Article  CAS  PubMed  Google Scholar 

  7. Rajkumar SV, Larson D, Kyle RA. Diagnosis of smoldering multiple myeloma. N Engl J Med. 2011;365(5):474–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kastritis E, Terpos E, Moulopoulos L, Spyropoulou-Vlachou M, Kanellias N, Eleftherakis-Papaiakovou E, et al. Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia. 2012;27:947.

    Article  PubMed  Google Scholar 

  9. Waxman AJ, Mick R, Garfall AL, Cohen A, Vogl DT, Stadtmauer EA, et al. Classifying ultra-high risk smoldering myeloma. Leukemia. 2014;29:751.

    Article  PubMed  Google Scholar 

  10. Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia. 2013;27(4):941–6.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood. 2008;111(2):785–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sorrig R, Klausen TW, Salomo M, Vangsted AJ, Ostergaard B, Gregersen H, et al. Smoldering multiple myeloma risk factors for progression: a Danish population-based cohort study. Eur J Haematol. 2016, 97(3):303–9.

    Google Scholar 

  14. Perez-Persona E, Vidriales MB, Mateo G, Garcia-Sanz R, Mateos MV, de Coca AG, et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood. 2007;110(7):2586–92.

    Article  CAS  PubMed  Google Scholar 

  15. Perez-Persona E, Mateo G, Garcia-Sanz R, Mateos MV, de Las Heras N, de Coca AG, et al. Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells. Br J Haematol. 2010;148(1):110–4.

    Article  PubMed  Google Scholar 

  16. Bianchi G, Kyle RA, Larson DR, Witzig TE, Kumar S, Dispenzieri A, et al. High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma. Leukemia. 2013;27(3):680–5.

    Article  CAS  PubMed  Google Scholar 

  17. Gonsalves WI, Rajkumar SV, Dispenzieri A, Dingli D, Timm MM, Morice WG, Lacy MQ, Buadi FK, Go RS, Leung N, Kapoor P, Hayman SR, Lust JA, Russell SJ, Zeldenrust SR, Hwa L, Kourelis TV, Kyle RA, Gertz MA, Kumar SK. Quantification of circulating clonal plasma cells (cPCs) via multiparametric flow cytometry (MFC) to identify patients with smoldering multiple myeloma (SMM) at high risk of progression. J Clin Oncol. 2016;34(Suppl.):Abstract 8015

    Google Scholar 

  18. Fernández de Larrea C, Isola I, Cibeira MT, Rosiñol L, Calvo X, Tovar N, et al. Smoldering multiple myeloma: impact of the evolving pattern on early progression. Blood. 2014;124(21):3363.

    Google Scholar 

  19. Rosinol L, Blade J, Esteve J, Aymerich M, Rozman M, Montoto S, et al. Smoldering multiple myeloma: natural history and recognition of an evolving type. Br J Haematol. 2003;123(4):631–6.

    Article  CAS  PubMed  Google Scholar 

  20. Ravi P, Kumar S, Larsen JT, Gonsalves W, Buadi F, Lacy MQ, Go R, Dispenzieri A, Kapoor P, Lust JA, Dingli D, Lin Y, Russell SJ, Leung N, Gertz MA, Kyle RA, Bergsagel PL, Rajkumar SV. Evolving changes in M-protein (M), quantitative involved immunoglobulin (Ig), and hemoglobin (Hb) to identify patients (pts) with ultra high-risk smoldering multiple myeloma (UHR-SMM). J Clin Oncol. 2016;34(Suppl.):Abstr 8004.

    Google Scholar 

  21. Dhodapkar MV, Sexton R, Waheed S, Usmani S, Papanikolaou X, Nair B, et al. Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120). Blood. 2014;123(1):78–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gonzalez-Calle V, Davila J, Escalante F, de Coca AG, Aguilera C, Lopez R, et al. Bence Jones proteinuria in smoldering multiple myeloma as a predictor marker of progression to symptomatic multiple myeloma. Leukemia. 2016;30:2026.

    Article  CAS  PubMed  Google Scholar 

  23. Merz M, Hielscher T, Wagner B, Sauer S, Shah S, Raab MS, et al. Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma. Leukemia. 2014;28:1902.

    Article  CAS  PubMed  Google Scholar 

  24. Zamagni E, Nanni C, Gay F, Pezzi A, Patriarca F, Bello M, et al. 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease. Leukemia. 2016;30(2):417–22.

    Article  CAS  PubMed  Google Scholar 

  25. Siontis B, Kumar S, Dispenzieri A, Drake MT, Lacy MQ, Buadi F, et al. Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: identification of patients needing therapy. Blood Cancer J. 2015;5:e364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rajkumar SV, Gupta V, Fonseca R, Dispenzieri A, Gonsalves WI, Larson D, et al. Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia. 2013;27:1738.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Neben K, Jauch A, Hielscher T, Hillengass J, Lehners N, Seckinger A, et al. Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load. J Clin Oncol. 2013;31(34):4325–32.

    Article  PubMed  Google Scholar 

  28. Khan R, Dhodapkar M, Rosenthal A, Heuck C, Papanikolaou X, Qu P, et al. Four genes predict high risk of progression from smoldering to symptomatic multiple myeloma (SWOG S0120). Haematologica. 2015;100(9):1214–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mailankody S, Korde N, Roschewski MJ, Christofferson A, Boateng M, Zhang Y, Manasanch EE, Kazandjian DG, Kwok M, Bhutani M, Tageja N, Zingone A, Costello R, Lamy L, Hultcrantz M, Papaemmanuil E, Stetler-Stevenson M, Figg WD, Keats JJ, Landgren O. Genetic plasma cell signatures in high-risk smoldering myeloma versus multiple myeloma patients. J Clin Oncol. 2016;34(Suppl.):Abstr 8003.

    Google Scholar 

  30. Muta T, Iida S, Matsue K, Sunami K, Isoda J, Harada N, et al. Predictive significance of serum beta 2-microglobulin levels and M-protein velocity for symptomatic progression of smoldering multiple myeloma. Blood. 2014;124(21):3379.

    Google Scholar 

  31. Hajek R, Sandecka V, Seckinger A, Spicka I, Scudla V, Gregora E, et al. Prediction of progression of Smouldering into therapy requiring multiple myeloma by easily accessible clinical factors [in 527 patients]. Blood. 2014;124(21):2071.

    Google Scholar 

  32. Mateos MV, San Miguel JF. New approaches to smoldering myeloma. Curr Hematol Malig Rep. 2013;8:270.

    Article  PubMed  Google Scholar 

  33. Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, Corral LL, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Arguiñano JM, Quintana N, García JL, Bladé J, Lahuerta JJ, Miguel JF. Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up a randomised, controlled, phase 3 trial. Lancet Oncol. 2016 [Epub ahead of print].

    Google Scholar 

  34. Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, et al. Treatment with Carfilzomib-Lenalidomide-dexamethasone with Lenalidomide extension in patients with smoldering or newly diagnosed multiple myeloma. JAMA Oncol. 2015;1(6):746–54.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Complejo Asistencial Universitario de Salamanca/Instituto Biosanitario de Salamanca (CAUSA/IBSAL), Paseo San Vicente, 58-182, 37007, Salamanca, Spain

    María-Victoria Mateos M.D., Ph.D.

  2. Clínica Universidad de Navarra, Navarra, Spain

    Jesús F. San-Miguel M.D., Ph.D.

Authors
  1. María-Victoria Mateos M.D., Ph.D.
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  2. Jesús F. San-Miguel M.D., Ph.D.
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Correspondence to María-Victoria Mateos M.D., Ph.D. .

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Editors and Affiliations

  1. Cancer Research Foundation, Chappaqua, New York, USA

    Peter H. Wiernik

  2. Cancer Research Foundation, Chappaqua, New York, USA

    Janice P. Dutcher

  3. Department of Hematology, Mayo Clinic Department of Hematology, Rochester, Minnesota, USA

    Morie A. Gertz

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Mateos, MV., San-Miguel, J.F. (2018). Smoldering Multiple Myeloma. In: Wiernik, P., Dutcher, J., Gertz, M. (eds) Neoplastic Diseases of the Blood. Springer, Cham. https://doi.org/10.1007/978-3-319-64263-5_26

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  • DOI: https://doi.org/10.1007/978-3-319-64263-5_26

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-64262-8

  • Online ISBN: 978-3-319-64263-5

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