New study supports more accurate identification of people at high risk of developing multiple myeloma

Researchers from the major iStopMM project are part of the team behind a new study shedding light on how best to identify the people at highest risk of developing active multiple myeloma, who could therefore benefit from early intervention. Their findings are presented in an article published recently in the prestigious journal JAMA Oncology.

Multiple myeloma is a an incurable bone marrow cancer that develops from precursor conditions over a number of years. The Iceland Screens, Treats and Prevents Multiple Myeloma project (iStopMM) is one of the largest research projects ever conducted in Iceland. Scientists at the University of Iceland and their colleagues have worked to identify the causes of the disease and studied the impact of screening for the precursor conditions. iStopMM is based on data from over 75,000 people in Iceland and has already revealed a number of interesting findings. Most recently, the team have discovered that there could be tens of thousands of people all over the world with smouldering multiple myeloma who have been classified as high risk for developing multiple myeloma, when in fact their real risk is considerably lower.

The study reported in JAMA Oncology addresses an important question regarding smouldering multiple myeloma – namely, how best to identify the people at greatest risk of developing active multiple myeloma, who may therefore benefit from early treatment.

“What is special about iStopMM for this research is that we have data on individuals who were diagnosed with smouldering multiple myeloma through screening, rather than due to symptoms or other clinical indications. This provides a unique opportunity to examine how risk assessment tools for precursor stages of multiple myeloma perform in the general population – research in this field has largely been based on individuals diagnosed within the healthcare system,” says Sigrún Þorsteinsdóttir, physician and postdoctoral researcher at the Faculty of Medicine, who is one of the authors of the article in JAMA Oncology. The research team also includes Cecilie Vælsø Mæng, PhD student at the University of Copenhagen, and Sigurður Yngvi Kristinsson, professor at the Faculty of Medicine and leader of iStopMM, as well as scientists from numerous other Nordic research institutions and universities.

In addition to data on smouldering multiple myeloma from the iStopMM study, the research team used data from DALY-CARE (Danish Lymphoid Cancer Resource), a database containing data on all individuals diagnosed with smouldering multiple myeloma within the Danish healthcare system from 2002 to 2025.

The study compared two methods for identifying which people with smouldering multiple myeloma are at highest risk of developing active multiple myeloma. The first method used criteria from the AQUILA clinical trial, which investigated the effects of early treatment with the drug daratumumab in individuals classified as having high-risk smouldering multiple myeloma. The second method applied the so-called 2/20/20 risk model.

“According to the AQUILA criteria, about three times as many people with smouldering multiple myeloma were classified as high risk compared with the 2/20/20 risk model. When we then examined the actual progression of the disease in the Danish cohort, it became clear that the 2/20/20 model identified a smaller group of individuals who were at much higher risk of developing active multiple myeloma. The findings therefore highlight how important it is to accurately define the high-risk group when assessing who may benefit from early treatment,” says Sigrún.

Research has shown that early intervention can benefit certain people with smouldering multiple myeloma, and daratumumab has now been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for high-risk smouldering multiple myeloma. ““This makes it increasingly important to accurately identify those who are most likely to benefit from treatment, while avoiding unnecessary treatment in people at lower risk of developing active multiple myeloma. This can spare patients unnecessary side effects and time-consuming treatment, while also avoiding substantial healthcare costs for treatments that may provide little benefit,”Sigrún explains.

The article in JAMA Oncology is available here.