ctDNA for risk stratification of SMM progression

At the 2026 European Hematology Association (EHA) Congress 2026 in Stockholm, Dr Sigrún Thorsteinsdóttir (University of Iceland & Rigshospitalet Copenhagen) presented data of a study evaluating the use of circulating tumor plasma cells (CTPCs) for risk stratification and monitoring in patients with smoldering multiple myeloma (SMM). The analysis was based on the iStopMM study, a large population-based screening initiative in Iceland that screened more than 72,000 individuals using M-protein measurements and free light chain analysis. Overall, this study identified approximately 3,500 cases of monoclonal gammopathy of undetermined significance (MGUS) and more than 200 cases of SMM.

The study assessed CTPCs using next-generation flow cytometry in peripheral blood samples obtained from 133 patients at the time of their SMM diagnosis. Detectable CTPCs were identified in approximately half of the cohort at baseline. Longitudinal follow-up data with repeated blood measurements were available for 107 patients. During follow-up, 14 patients progressed to multiple myeloma (N=12) or AL amyloidosis (N=2). Using a cutoff of 0.001% to define CTPC positivity, investigators found that 13 of the 14 patients who experienced clinical progression had detectable CTPCs prior to progression. In addition, 20 patients who were CTPC-negative at diagnosis became positive during follow-up, indicating that the CTPC status may change over time.

The findings demonstrate that CTPCs are predictive of disease progression both at diagnosis and during follow-up. The results further suggest that CTPCs represent a dynamic biomarker that may be useful for longitudinal monitoring of patients with SMM. This approach could potentially reduce the need for invasive bone marrow assessments while helping to identify individuals at higher risk of progression and patients with a very low likelihood of disease progression.