Identifying High-Risk Smoldering Multiple Myeloma for Early Intervention
Menée à partir de données portant sur 1 340 personnes (âge médian : 70, 72 ans selon le groupe ; 52 à 60 % de femmes selon le groupe), cette étude examine les taux de patients présentant un risque élevé de myélome multiple en fonction de la définition utilisée (critères d'inclusion de l'essai Aquila ou modèle de stratification 2/20/20)
Importance : Early treatment may benefit patients with high-risk smoldering multiple myeloma (SMM), a precursor of active multiple myeloma, but inconsistent high-risk definitions may capture different disease subsets.
Objective : To compare 2 high-risk SMM risk definitions: the AQUILA trial inclusion criteria and the 2/20/20 risk stratification model.
Design, Setting, and Participants : This cohort study included data from 2 separate SMM cohorts and a retrospective analysis assessing progression risk. The Iceland Screens, Treats, and Prevents Multiple Myeloma (iStopMM) is a large population-based screening study in Iceland, conducted from 2016 to 2021, while the Danish Lymphoid Cancer Resource (DALY-CARE) is a nationwide clinical data collection from Denmark from 2002 to 2025. From the iStopMM cohort, individuals with SMM were detected by screening. In DALY-CARE, individuals with SMM were identified in a clinical setting. Data were analyzed from March 2025 to January 2026.
Exposure : High-risk SMM by the AQUILA criteria, defined by presence of immunoparesis, monoclonal protein (M-protein) greater than 3.0 g/dL, immunoglobin A isotype, bone marrow plasma cell infiltration greater than 50%, or free light chain ratio 8 or greater. High risk by the 2/20/20 model was defined by presence of more than 1 of: M-protein greater than 2.0 g/dL, bone marrow plasma cell infiltration greater than 20%, or free light chain ratio greater than 20.
Main Outcomes and Measures : Proportion of high-risk SMM in the 2 cohorts by both models and risk of progression as defined by initiation of treatment.
Results : A total of 193 individuals (median [IQR] age, 70 [63-72] years; 116 [60%] female) from the iStopMM cohort and 1147 individuals (median [IQR] age, 72 [64-79] years; 598 [52%] female) from the DALY-CARE cohort were included. In the screened cohort (iStopMM), 65 participants (34%) had high-risk SMM according to the AQUILA criteria, and 15 participants (8%) had high-risk SMM according to the 2/20/20 model. In the clinical cohort (DALY-CARE), 607 participants (55%) met high-risk criteria according to AQUILA, and 219 participants (19%) had high-risk SMM according to the 2/20/20 model. For individuals with AQUILA-defined high-risk disease in the clinical cohort, the 2-year progression risk was 27.0% (95% CI, 23.3%-30.7%), with an annual progression rate of 14.5%. For individuals with high risk defined by 2/20/20, the 2-year progression risk was 44.1% (95% CI, 37.1%-51.1%), with an annual progression rate of 27.3%.
Conclusions and Relevance : This cohort study found that the AQUILA trial criteria classified approximately 3 times more patients with SMM as having high risk compared with the 2/20/20 model and captured a group with substantially lower progression risk. These results suggest that the 2/20/20 model more accurately identifies a truly high-risk group with SMM, for whom early treatment is more likely to be beneficial.
JAMA Oncology , résumé, 2026