OAB-037: Assessing the prognostic utility of the Mayo 2018 and IMWG 2020 smoldering multiple myeloma risk stratification scores applied post diagnosis

Abstract

<h3>Background</h3> Smoldering multiple myeloma (SMM) prognostication models routinely used in clinical practice were developed for use at diagnosis. However, retrospective studies in SMM patients have shown that the risk of progression to multiple myeloma (MM) decreases over time. Therefore, this study assessed whether the Mayo 2018 and IMWG 2020 scores could be used dynamically to risk stratify patients post-diagnosis, and whether they could identify SMM patients with evolving disease markers. <h3>Methods</h3> We retrospective studied 704 SMM patients diagnosed between January 2000 to January 2020. Patients with a baseline FLCr ≥100 and involved FLC ≥10 mg/dL or baseline bone marrow plasma cells ≥60% were excluded. We collected serial laboratory data and re-applied the Mayo 2018 and IMWG 2020 SMM risk stratification models at annual landmark timepoints up to 4 years post SMM diagnosis. Survival analyses were performed using the Kaplan-Meier method. Time to progression was defined as time from diagnosis or landmark timepoint to treatment initiation for MM or systemic AL amyloidosis. <h3>Results</h3> At SMM diagnosis, 271 (38%) patients were low risk, 228 (32%) were intermediate risk, and 205 (29%) were high risk per the Mayo 2018 score. Applying the IMWG 2020 score at diagnosis, 90 (34%) of patients were low risk, 111 (42%) were low-intermediate risk, 54 (21%) were intermediate risk, and 9 (3%) were high risk. The Mayo 2018 and IMWG 2020 risk scores was re-assessed annually post-diagnosis in patients without progression (respective sample sizes: n=430 and n=197 at year 1 landmark, n=326 and n=143 at year 2 landmark, n=260 and n=106 at year 3 landmark, n=203 and n=73 patients at year 4 landmark). The Mayo 2018 and IMWG 2020 models reliably stratified patients based on progression risk post diagnosis; the respective 2-year progression risk in Mayo 2018 high-risk versus IMWG 2020 intermediate-high risk patients was 51% versus 62% at the 1-year landmark, 60% versus 65% at the 2-year landmark, 47% versus 62% at the 3-year landmark, and 47% versus 45% at the 4-year landmark. Patients evolving to a higher Mayo 2018 or IMWG 2020 risk category during follow up consistently had an increased risk of progression compared to patients with a stable/decreased risk categorization. We showed that patients categorized as Mayo 2018 high-risk at follow-up had a similar risk of progression regardless of whether the baseline risk categorization was low-intermediate versus high-risk (HR 0.87, 95% CI 0.51-1.48, p=0.606 at 2-year landmark; HR 1.01, 95% CI 0.59-1.73, p=0.972 at 3-year landmark; HR 0.75, 95% CI 0.34-1.65, p=0.467 at 4-year landmark). <h3>Conclusion</h3> Our findings support the use of the Mayo 2018 and IMWG 2020 scores post-diagnosis. We showed that patients migrating to a higher risk category have an increased risk of progression, suggesting that patients evolving to a high-risk score during follow-up should be considered for early intervention treatment approaches.