(PA-357) The Natural History of Smoldering Multiple Myeloma (SMM): Evolution of Incidence and Progression Risk from 2005 to 2022 in a Nationwide Danish Population-Based Cohort

Smoldering Multiple Myeloma (SMM) is an asymptomatic precursor to Multiple Myeloma (MM) and is usually diagnosed during work-up of suspected malignancy, bone disease, neuropathy, or other unspecific symptoms. Due to changes in diagnostic criteria for MM, increased sensitivity and availability of diagnostic tools, shifting population demographics, and greater disease awareness, the characteristics and progression risk of SMM have likely evolved in the last decades. In the present study, we aimed to describe changes over time of SMM incidence, progression risk, and overall survival in a population-based cohort.

Methods: We used nationwide data from the Danish Lymphoid Cancer Research (DALY-CARE) resource, including the Danish National Multiple Myeloma Registry. We defined SMM as individuals with a ICD coded diagnosis of MM that did not receive anti-myeloma treatment and did not die within 90 days of first registered diagnosis. The cohort was stratified according to year of diagnosis: 2005-2011, 2012-2015, or 2016-2022. Progression was defined as the first day of anti-myeloma treatment. Overall survival was calculated using Kaplan Meier estimation. Finally, progression risk was examined by 2- and 5-year cumulative incidence of progression with death as competing risk using Aalen-Johanson estimation

Results:

A total of 2,461 individuals with SMM diagnosed from 2005 to 2022 were identified. The median follow-up time was 3.5 (IQR: 1.6-6.6) years. The yearly incidence of SMM doubled from approximately 1.9 cases/100,000 in 2005 to 4.0 cases/100,000 in 2022. The cohort diagnosed in 2016-2022 was slightly older (median age 74(IQR: 67-80)) compared to the previous cohorts (median age 72 years (64-80)) and had more males (57% vs 50%). The median overall survival increased from 5.5 years (95%CI: 5.1-5.9) for individuals diagnosed from 2005-2011 to 7.7 years (95%CI: 7.0-8.5) for individuals diagnosed in 2012 or later. The 2-year cumulative incidence of progression decreased from 27.6% (95%CI: 24.3-30.9) if diagnosed 2005-2011, to 18.2% (95%CI: 16.0-20.6) in 2016-2022. Lastly, the 5-year cumulative incidence of progression decreased from 34.3% (95%CI: 30.7-37.8) if diagnosed 2005-2011, to 28.0% (95%CI: 25.0-30.9) in 2016-2022.

Conclusions:

This large population-based study on SMM demonstrates that the risk of progression from SMM to MM has decreased and overall survival has increased over time. These changes likely reflect updated definitions of diagnostic criteria for MM as well as more sensitive diagnostics. In addition, we found that the incidence of SMM increased during the study period, most likely due to a combination of factors including increased M-protein testing and ageing population. These results are important considering recent clinical trials indicating that treatment could be beneficial for selected individuals with SMM and highlights the importance of risk stratification in the management of SMM to optimize both patient care and healthcare resource utilization.