The level of monoclonal protein (MP) and bone marrow plasma cells (BMPCs) at diagnosis and dynamic changes in MP and free light chain ratio (FLCr) during follow-up were independently associated with progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to the results of a retrospective study published in the American Journal of Hematology.

Several prediction models for SMM progression to MM have been proposed and are typically based on a combination of biomarkers at diagnosis, such as level of MP, BMPCs, and FLCr. Evolving MP has also been proposed as a potential predictive biomarker. The purpose of this study was to evaluate biomarkers among patients with SMM who have or have not progressed to MM.

The retrospective study included 126 patients with SMM, including 44 who had progressed to MM. MP and FLC were evaluated approximately every 2 months. Data from electronic medical records were used to assess demographics, imaging, and date of progression. The median follow-up was 4.5 years.

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Confirming prior studies of prediction models at diagnosis, MP >20 g/L and BMPC >20% alone or together were independent risk factors for progression to MM, with a significantly shorter time to progression (TTP) compared with patients who had no risk factors (P =.006 vs 1 risk factor; P =.011 1 risk factor vs 2 risk factors).

Evolving MP of higher than 5 g/L combined with evolving involved/uninvolved FLCr of greater than 4.5 were also significantly associated with a shorter TTP (P <.001). Evolving MP and/or FLCr occurred among 82% of patients who progressed compared with 30% of patients who did not experience progression. The median time to progression once an evolving MP or FLCr was identified was 5 months (range, 2-38 months).

The authors concluded that “the findings in our retrospective study support that dynamic changes in MP can identify patients at high risk of progression.” They added, however, that “as these findings are exploratory, they should be validated in future prospective studies.”


Gran C, Luong V, Bruchfeld JB, et al. Dynamic follow-up of smoldering multiple myeloma identifies a subset of patients at high risk of progression. Am J Hematol. Published online December 2, 2020.