Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1.1 years (95% CI 0.5–2.0) and progression rate at 3 years was 71%. Development of the evolving type drastically worsened the prognostic estimation made at diagnosis for every covariate predictive of progression (serum M-protein size, bone marrow plasma cell infiltration, immunoparesis and Mayo Clinic risk). On average, the hazard ratio for progression to symptomatic MM increased to 5.1 (95% CI 3.4–7.6) after recognition of the evolving type. In conclusion, in patients with SMM the evolving pattern accurately predicts the risk of early progression to symptomatic disease, thereby allowing the identification of ultra-high risk patients who would be candidates for immediate therapy.

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We would like to thank Esther Bladé for her technical support in this research. This work has been supported in part by grants PI16/0423 and PI12/1093 from Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” and 2014SGR-552 from Agència de Gestió d’Ajuts Universitaris i de Recerca (Generalitat de Catalunya).

Author contributions

C.F.L. and I.I. designed the study, collected and analyzed data, performed statistical analysis, wrote and reviewed the paper; A.P. analyzed data, performed statistical analysis, wrote and reviewed the paper; M.C., L.G.L.R., and N.T. collected data and reviewed the paper; X.C. and L.M. collected data, reviewed bone marrow aspirates and reviewed the paper; M.R. reviewed bone marrow aspirates and reviewed the paper; J.I.A., E.L., T.D., and J.Y. collected data, performed laboratory assays and reviewed the paper; L.R. and J.B. analyzed data and reviewed the paper.

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    1. Department of Hematology, Amyloidosis and Myeloma Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain

      • Carlos Fernández de Larrea
      • , Ignacio Isola
      • , Ma Teresa Cibeira
      • , Natalia Tovar
      • , Luis-Gerardo Rodríguez-Lobato
      • , Tania Díaz
      • , Ester Lozano
      • , Joan Bladé
      •  & Laura Rosiñol
    2. Department of Hemotherapy and Hemostasis, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain

      • Arturo Pereira
    3. Department of Hematopathology, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain

      • Laura Magnano
      • , Xavier Calvo
      •  & María Rozman
    4. Department of Immunology, Amyloidosis and Myeloma Unit, Hospital Clínic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain

      • Juan I. Aróstegui
      •  & Jordi Yagüe


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    Correspondence to Joan Bladé.

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