Epidemiology Unknown: Developing an Approach to Identify Potential Smoldering Multiple Myeloma Cases
Authors: Fatoki Raleigh A. , Carpenter Diane M. , Khan Adnan , Stevenson Ryan , Lo Joan C. , Baer David M. 
Published: November 2021

Abstract
Background
Smoldering Multiple Myeloma (SMM) is an asymptomatic clonal plasma cell disorder that identifies patients at risk for progression to Multiple Myeloma (MM). The standard of care for SMM has traditionally been observation, but some cancer centers are now treating high-risk SMM before progression to MM. The diagnostic criteria for SMM have also changed in recent years, and current estimates of SMM are derived from large MM databases and observations from tertiary centers. The goal of this study was to develop an approach for identifying SMM cases in a large integrated healthcare delivery system to better characterize the epidemiology of SMM in community-based populations.
Methods
This retrospective, observational study was conducted in Kaiser Permanente Northern California (KPNC) using KPNC SEER-based Cancer Registry data and information from the electronic health record (EHR). Potential SMM cases from 1/1/2010 to 12/31/2018 were identified using three approaches: Group 1 - identified via the KPNC Cancer Registry based on indicators of 'asymptomatic myeloma', 'evolving myeloma', and 'smoldering myeloma'; Group 2 - identified via the KPNC Cancer Registry as MM cases who had a physician visit note containing the word 'smoldering' but did not begin treatment within 1 year of diagnosis; Group 3 - identified via the KPNC Cancer Registry as MM cases who had a physician visit note containing the word 'smoldering' but did begin treatment within 1 year of diagnosis. Chart review was performed for these potential SMM cases (Groups 1-3) to document initial bone marrow biopsy results (bone marrow plasma cell percentage, BMPC) and skeletal findings (presence or absence of lytic bone lesions) around the time of biopsy. When BMPC was reported as a range, the highest value was captured. Patient demographics (age, sex and race/ethnicity) were obtained from the EHR. Bivariate analyses were performed using the chi-squared test and the Wilcoxon-Mann-Whitney nonparametric test. For binomial comparisons by mode of potential SMM case identification, Groups 1 and 2 were combined and compared to Group 3.
Results
A total of 471 potential SMM cases were identified, including 178 (37.8%) via Group 1, 35 (7.4%) via Group 2, and 258 (54.8%) via Group 3 (Figure). The median age was 71 years (interquartile range, IQR 62-78) and 40.0% were female. The racial/ethnic distribution included 57.1% White, 17.6% Black, 10.8% Hispanic, 13.6% Asian, and 0.9% other/unknown race. There were no significant differences across groups (Group 1+2 vs Group 3) with respect to age (p=0.07), sex (p=0.85), or race/ethnicity (p=0.81).
There were 442 (93.8%) who underwent bone marrow biopsy. Among those with BMPC data, the median BMPC for Group 1 was 20.0% (IQR 10.0%-28.0%); for Group 2 was 25.0% (IQR 12.5%-50.0%), for Group 3 was 28.0% (IQR 15.0%-50.0%) (p&lt;0.001 comparing Groups 1+2, combined median 20.0%, IQR 10.0%-30.0%, vs Group 3, 28.0%, IQR 15.0%-50.0%). The proportion with BMPC ≥60% was 4%, 13%, and 22% for Groups 1, 2, and 3, respectively (Figure).
There were 413 (87.7%) who had skeletal imaging (n=405, 86.0% with available results) within 6 months of diagnosis. Of those with imaging results available to view, n=68 were found to have lytic lesions; 7.6% among Group 1, 6.9% among Group 2, 24.9% among Group 3 (p&lt;0.001 comparing Groups 1+2, 7.5%, vs Group 3, 24.9%).
Discussion
This study used a multifaceted approach to identify potential SMM cases from a large real-world clinical population in an integrated health system. We used an approach similar to prior SMM epidemiological studies and also included those with physician visit notes specifically containing the word 'smoldering' within the text. The vast majority of our cohort had BMPC between 10 and 60%, but those who received treatment within 1 year had greater BMPC and a higher proportion of lytic lesions. This suggests those who received treatment, Group 3, may have actually had a MM diagnosis, and physician visit notes containing the word 'smoldering' may have been intended to communicate something other than a SMM diagnosis. Further analyses will determine the effectiveness of each approach by confirming SMM cases according to the International Myeloma Working Group diagnostic criteria with incorporation of laboratory data and additional clinical findings. Among confirmed cases of SMM, the rate of progression to MM and the severity of end-organ damage at time of progression will be assessed.
Figure 1 Figure 1.

Disclosures
Lo: Novartis: Research Funding; Bristol-Myers-Squibb: Research Funding; CSL-Bering: Research Funding.