Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder with a heterogeneous risk of progression to symptomatic multiple myeloma (MM). Accurate risk stratification is crucial, particularly for identifying patients at high risk of progression within two years, as this group may benefit from early therapeutic intervention. Timely recognition of these high-risk individuals enables the initiation of treatment strategies aimed at delaying disease progression and improving clinical outcomes, while avoiding overtreatment in lower-risk patients.

To compare the risk classification outcomes of three established prognostic models—the Mayo Clinic 2018 '20/2/20′ criteria, the International Myeloma Working Group (IMWG) risk score, and the Pangea model—in a cohort of SMM patients from a Latin American reference center. Additionally, we classified the patients according to the high-risk SMM definition proposed by the Aquila study.

We conducted a retrospective analysis of 84 patients diagnosed with SMM at a Latin American reference center. Patients were stratified into risk categories according to three established prognostic models. For each model, we recorded the number and proportion of patients classified as high risk. We then evaluated the concordance among models, as well as discrepancies in risk classification, to assess the level of agreement and potential clinical implications of model selection.

Among the 84 patients included in the cohort, the median age was 64 years (IQR 57–74), with a predominance of females (61%). A non-IgG isotype was observed in 34% of cases. The median bone marrow plasma cell infiltration was 15% (IQR 11–20), the median serum monoclonal protein concentration was 14 g/L (IQR 9–22), and the median involved/uninvolved free light chain ratio was 3.4 (IQR 2.1–7.8). Overall, 12% of patients (95% CI: 7–20%) progressed to symptomatic multiple myeloma within two years. Based on risk stratification models, the Mayo Clinic 2018 criteria identified 16 patients (19%) as high risk, while the IMWG model classified 10 patients (11%) in this category. The Pangea model identified 7 patients (8%) with an estimated two-year progression risk of 25% or greater. Notably, according to the high-risk SMM definition proposed by the Aquila study, 48 patients (57%) in this cohort would meet criteria for high-risk disease.

As anticipated, the criterion employed by the Aquila study tends to overestimate the proportion of patients classified as having high-risk smoldering multiple myeloma (SMM). Although the Mayo Clinic, IMWG, and Pangea models demonstrated some variability, all provided risk estimates that fell within the confidence interval observed in this cohort. In resource-constrained settings, judicious allocation of healthcare resources is essential, and when therapies for SMM are available, they should be prioritized for patients identified as having high-risk disease.