14.4. The prognostic value of changes in monoclonal protein concentration

Chapter 14

Several studies have evaluated the prognostic impact of an increasing monoclonal protein concentration during follow-up on risk of SMM progression. Many [302][275][310], but not all studies [306], have reported a higher risk in patients who demonstrate a progressive rise in serum monoclonal protein. For example, Fernandez de Larrea et al. [302] studied 207 SMM patients, and defined an "evolving" monoclonal protein type as either a 10% increase within 6 months of diagnosis (for patients with an initial monoclonal protein ≥30 g/L) or a progressive increase in consecutive annual measurements during a period of 3 years (for patients with an initial monoclonal protein <30g/L). A quarter of patients displayed an evolving type, and this was associated with significantly shorter median time to progression (19.4 vs 3 years, p<0.001). The authors concluded that SMM should be routinely monitored for an evolving type during follow-up.

International guidelines recommend that serum protein electrophoresis and 24-hour urine electrophoresis are performed at SMM diagnosis and at 2 - 3 months. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6 - 12 months (Section 25.3.2). Whilst there are no recommendations for the frequency of sFLC analysis during follow-up, in a recent review article, Rajkumar [306] suggested that sFLCs should be evaluated every 3 - 4 months. This information can then be used to identify SMM patients at the highest risk of disease evolution [955].


  1. How frequently are sFLC ratios abnormal in SMM?
  2. What is the recommended management for a patient with 20% BMPCs, Freelite κ sFLCs 250 mg/L, λ sFLCs 2 mg/L (κ/λ sFLC ratio 125) and no evidence of myeloma-related end organ damage?


  1. An abnormal sFLC ratio is found in 74 - 90% of SMM patients at diagnosis (Section 14.2).
  2. An involved/uninvolved Freelite sFLC ratio of ≥100 (with involved sFLCs ≥100 mg/L) is considered a biomarker of malignancy. This patient would be classified as having active MM requiring treatment, even in the absence of myeloma-related symptoms (Section 14.1).