Incidence and Prevalence of Clinically Detected Smoldering Multiple Myeloma Among the General Population

Introduction:

Emerging data shows that early therapeutic intervention in patients with high risk smoldering multiple myeloma (SMM) may improve outcomes. While treatment of high-risk SMM is not standard of care in Canada, understanding the epidemiology of SMM in our region is important to contextualize the future healthcare resource implications of SMM treatment. Therefore, this study’s primary aim was to assess the incidence and prevalence of clinically- detected SMM among the general population over time, diagnosed as part of routine standard of care. Though a recent population-level screening study has shown that among screened patients, the prevalence of SMM in the general population over 40 years old is 0.53% (Thorsteindottir et al. BCJ 2023), we hypothesize that the prevalence of clinically-detected SMM population will be much lower.

Methods:

This retrospective observational study included all patients in the Champlain Local Health Integration Network (LHIN) found to have an abnormal monoclonal protein (MCP) (an abnormal serum or urine protein electrophoresis or immunofixation, or free light chain [FLC] ratio) between January 1, 2010, and December 31, 2022. Charts were reviewed to identify patients initially diagnosed with or progressing to SMM. Healthcare services in Ontario, Canada are provided through regional LHINs. The Ottawa Hospital is the only tertiary care and hematology referral center in the Champlain LHIN, therefore, we assumed that all incident cases of SMM were evaluated at our center and included in this study. To provide population-based incidence and prevalence rates of SMM, the adult population of individuals living within the Champlain LHIN was taken from the published 2016 and 2021 census data. The incidence of SMM was defined as the date a patient met clinical criteria for SMM (bone marrow [BM] plasma cells 10-59% in the absence of myeloma defining events [MDE], or MCP ≥30 g/L and no MDE if no bone marrow performed). The prevalence of SMM was defined as the number of patients actively followed for SMM at our institution during the relevant time-period. The date of last follow up was July 1, 2024.

Results:

A total of 5948 people had an abnormal MCP between 2010-2022, of whom 229 (3.9%) were diagnosed with SMM. Of the 229 SMM patients, the initial diagnosis was MGUS in 74 (32%) and SMM in 155 (68%) patients. Among the 229 SMM patients, 9 (4%) met criteria for high risk SMM based on the Mayo 20/20/20 score (Lakshman et al. BCJ 2018). However, given the initial lack of availability of the FLC test during the entire study period, FLC data was missing in 82 (36%) of patients. Among SMM patients, the median MCP at the time of first evaluation was 17.7 (IQR 10.3-29.5) g/L if diagnosed between 2010-2014, 13.5 (IQR 6.7-21.9) if diagnosed between 2015-2019, and 9.3 (IQR 3.5-14.4) g/L if evaluated between 2020-2022. A baseline BM evaluation was performed among 79% (n=46) and 94% (n=157) of patients diagnosed with SMM between 2010-2014 (n=62) and 2015-2022 (n=167), respectively. Overall, 108 (47%) of SMM patients were alive and had been clinically evaluated since July 1, 2023.

The incidence of SMM among per 100,000 people in the general population (n=1,230,655 in 2011; n=1,292,639 in 2016; n=1,394,070 in 2021) increased from 0.5 cases in 2011, to 0.9 cases in 2016, to 1.4 cases in 2021. If restricting to only people aged ≥40, the incidence of SMM per 100,000 people in the general population (n=623,370 in 2011, n=670,195 in 2016, and n=719,920 in 2021) was 1 case in 2011, 1.8 cases in 2016 and 2.8 cases in 2021. The prevalence of SMM per 100,000 people in the general population was 6.9 cases in 2011 (n=21), 7.7 (n=58) in 2016, and 11.3 (n=114) in 2021. The incidence of SMM among patients with an abnormal MCP increased from 1.6% (n=6 SMM; n=378 abnormal MCP) in 2011, 2.8% (n=12 SMM; n=12 abnormal MCP) in 2016, to 4.1% (n=20 SMM; n=486 abnormal MCP) in 2021.

Conclusion:

This large study shows that the prevalence of clinically-detected SMM among adults above age ≥40 is lower than reported in a universally screened patient population. While the incidence of SMM among patients with an abnormal MCP and among the general population has increased over time, the abnormal MCP size at diagnosis has decreased over time. This suggests that clinicians are more thoroughly evaluating patients for SMM even with smaller MCPs. Larger cohort studies are needed to evaluate if the incidence of clinically detected high-risk SMM has also increased over time.