November 4, 2021

Today marked the release of hundreds of abstracts or summaries of research studies that will be presented at the 63rd American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia, December 11-14. The myeloma community eagerly awaits this news each year to see what new findings might be on the horizon. The IMF is excited to report that the results from the IMF-supported iStopMM study will take center stage at ASH as no less than four abstracts will be presented in oral sessions, plus two more as posters. From the screening of the Icelandic population over the age of 40, serum sample results from over 75,000 individuals are enabling the Iceland-based research team led by Dr. Sigurdur Kristinsson (University of Iceland) to shed much-needed light on the early development of myeloma. 

History of iStopMM 

Launched in 2016, iStopMM is the first population-based screening study for MGUS. The study randomizes patients into three cohorts, including detailed diagnostic evaluation as well as early treatment intervention. The initial findings in over 3,000 newly detected MGUS patients reveal a much higher number of individuals with smoldering multiple myeloma (SMM) or even full-blown myeloma than anticipated. This indicates that early detection and intervention are achievable goals. Although very encouraging, further follow-up is required to demonstrate the full impact and make sure there are no major psychosocial or quality-of-life issues for individuals who are part of this screening project. 

Occurrence of smoldering multiple myeloma (SMM) 

For the first time, it is demonstrated that the prevalence of SMM in a screened population is 0.5%: much higher than expected. In addition, approximately one-third of the SMM patients have intermediate or high-risk disease, indicating the potential need for early intervention, and an outcomes benefit from this early intervention. Through the IMF’s International Myeloma Working Group (IMWG), the risk-scoring for high-risk SMM has been refined. The iStopMM results underscore the need and value of increasingly refined scoring systems. 

COVID-19 in Iceland 

As part of the iStopMM screening process, COVID-19 testing was performed. In this very large group of individuals, there turned out to be NO increased susceptibility to COVID-19 infection (versus the rest the of Icelandic population). This implies that the profound immune compromised state that is characteristic of active myeloma is NOT present in patents with MGUS and very early disease but emerges as part of the progression to more advanced diseases. This is very reassuring for patients with early disease and points to a need for detailed immunological studies during disease evolution. MGUS is clearly not such a high-risk group as previously assumed. 

Diagnosis of monoclonal gammopathies in individuals with reduced kidney function

The traditional diagnosis of MGUS and other monoclonal gammopathies relies on the levels of free light chain proteins in the blood. Since free light chain levels go up as part of the impaired kidney function, it has been difficult to define accurate reference levels for free light levels indicative of confirmed MGUS. As a result of data from the iStopMM study, new reference ranges are proposed that can lead to much more accurate diagnoses in individuals with reduced kidney function. 

The potential of powerful population-based studies 

These four studies illustrate what can be learned to better understand and manage early disease. It is likely that an ultimate recommendation will be that screening is so helpful that it is an appropriate early tool for the management monoclonal plasma cell disorders. Much more information is to come, including the role of mass spectrometry as part of screening, as well as the DNA sequencing details of those individuals with and without MGUS, which will be an especially revealing analyses. So, stay tuned as additional important data emerge in the coming months and years. Congratulations to the amazing and dedicated iStopMM Team leading the way to the future! 

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