The diagnosis of smoldering multiple myeloma (SMM) includes patients with a heterogeneous risk of progression to active multiple myeloma (MM): some patients will never progress, whereas others will have a high risk of progression within the first 2 years. Therefore, it is important to improve risk assessment at diagnosis. We conducted a retrospective study in a large cohort of SMM patients, in order to investigate the role of Bence Jones (BJ) proteinuria at diagnosis in the progression to active MM. We found that SMM patients presenting with BJ proteinuria had a significantly shorter median time to progression (TTP) to MM compared with patients without BJ proteinuria (22 vs 88 months, respectively; hazard ratio=2.3, 95% confidence interval=1.4–3.9, P=0.002). We also identified risk subgroups based on the amount of BJ proteinuria: ⩾500 mg/24 h, <500 mg/24 h and without it, with a significantly different median TTP (13, 37 and 88 months, P<0.001). Thus, BJ proteinuria at diagnosis is an independent variable of progression to MM that identifies a subgroup of high-risk SMM patients (51% risk of progression at 2 years) and ⩾500 mg of BJ proteinuria may allow, if validated in another series, to reclassify these patients to MM requiring therapy before the end-organ damage development.
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Kyle RA, Child JA, Anderson K, Barlogie B, Bataille R, Bensinger W et al. 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: 749–757.
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: 538–548.
Kyle RA, Remstein ED, Therneu TM, Dispenzieri A, Kurtin PJ, Hodnefield JM et al. Clinical course and prognosis of smoldering multiple myeloma. N Engl J Med 2007; 356: 2582–2590.
Pérez-Persona E, Vidriales MB, Mateo G, García-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: 2586–2592.
Leung N, Behrens J . Current approach to diagnosis and management of acute renal failure in myeloma patients. Adv Chron Kidney Dis 2012; 19: 297–302.
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: 842–854.
Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, López Corral L et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 2013; 369: 438–447.
Kristinsson SY, Holmberg E, Blimark C . Treatment for high-risk smoldering myeloma. N Engl J Med 2013; 369: 1762–1765.
Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Melton LJ, Benson JT et al. Clinical course of light-chain smouldering multiple myeloma (idiopathic Bence Jones proteinuria): a retrospective cohort study. Lancet Haematol 2014; 1: 28–36.
López-Corral L, García-Sanz R, San Miguel JF . Value of serum free light chains assay in plasma cell disorders. Med Clin (Barc) 2010; 135: 368–374.
Singhal S, Stein R, Vickrey E, Mehta J . The serum-free light chain assay cannot replace 24-hour urine protein estimation in patients with plasma cell dyscrasias. Blood 2007; 109: 3611–3612.
Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc 2006; 81: 1575–1578.
Hill PG, Forsyth JM, Rai B, Mayne S . Serum free light chains: an alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies. Clin Chem 2006; 52: 1743–1748.
Abraham RS, Clark RJ, Bryant SC, Lymp JF, Larson T, Kyle RA et al. Correlation of serum immunoglobulin free light chain quantification with urinary Bence Jones protein in light chain myeloma. Clin Chem 2002; 48: 655–657.
Nowrousian MR, Brandhorst D, Sammet C, Kellert M, Daniels R, Schuett P et al. Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma. Clin Cancer Res 2005; 11: 8706–8714.
Beetham R, Wassell J, Wallage MJ, Whiteway AJ, James JA . Can serum free light chains replace urine electrophoresis in the detection of monoclonal gammopathies? Ann Clin Biochem 2007; 44: 516–522.
Sørrig R, Klausen TW, Salomo M, Vangsted AJ, Østergaard B, Gregersen H et al. Smoldering multiple myeloma risk factors for progression: a Danish population-based cohort study. Eur J Haematol 2015; e-pub ahead of print 29 December 2015; doi:10.1111/ejh.12728.
Waxman AJ, Mick R, Garfall AL, Cohen A, Vogl DT, Stadtmauer EA et al. Classifying ultra-high risk smoldering myeloma. Leukemia 2015; 29: 751–753.
Tate JR, Mollee P, Dimeski G, Carter AC, Gill D . Analytical performance of serum free light-chain assay during monitoring of patients with monoclonal light-chain diseases. Clin Chim Acta 2007; 376: 30–36.
Tate Daval S, Tridon A, Mazeron N, Ristori JM, Evrard B . Risk of antigen excess in serum free light chain measurements. Clin Chem 2007; 53: 1985–1986.
Solomon A, Weiss DT, Kattine AA . Nephrotoxic potential of Bence Jones proteins. N Engl J Med 1991; 324: 1845–1851.
Weber DM, Dimopoulos MA, Moulopoulos LA, Delasalle KB, Smith T, Alexanian R . Prognostic features of asymptomatic multiple myeloma. Br J Haematol 1997; 97: 810–814.
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 111: 785–789.
We thank all the investigators and patients for their participation in this study.
MVM conceived the idea and together with VGC designed the study. VGC, JD, FE, AGC, CA, RL, AB, JMA, RH, JMH and PF provided the data acquisition. VGC and MVM developed the analysis and interpretation of data. VGC drafted the article under the supervision of MVM. MVM, NP, EMO, NG and RGS revised it critically and gave final approval of the version to be submitted. All authors of this paper have read and approved the final version submitted.
The authors declare no conflict of interest.
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González-Calle, V., Dávila, J., Escalante, F. et al. Bence Jones proteinuria in smoldering multiple myeloma as a predictor marker of progression to symptomatic multiple myeloma. Leukemia 30, 2026–2031 (2016) doi:10.1038/leu.2016.123
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