(PA-333) Improved Survival in Multiple Myeloma Following Prior Detection of Precursor Conditions: A Nationwide Real-world Study

Multiple myeloma typically evolves from precursor conditions: monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (smolMM).  Although diagnostic tools such as peripheral blood electrophoresis allow for less invasive screening, the value of identifying these precursors remains debated, primarily because treatment is deferred until symptomatic MM (symMM). The critical question is whether early detection of precursor conditions confers survival benefits, especially given evidence that clonal evolution intensifies as the disease progresses. 
 

 

 

Methods:

Using Korea's Health Insurance Review and Assessment Service database, which covers virtually the entire Korean population,  we conducted a nationwide retrospective study to answer this question. We identified patients newly diagnosed with MGUS (n = 5,500) or multiple myeloma (n = 17,809) from 2009-2022 and classified them into three cohorts (Figure S1): the MGUS to symMM cohort (n = 220), consisting of patients who progressed from MGUS to symMM; the smolMM to symMM cohort (n = 447), consisting of patients who progressed from smolMM to symMM; and the de novo symMM cohort (n = 15,067), comprising patients diagnosed directly with symMM without preceding MGUS or smolMM diagnoses.

We defined the index date for survival analysis as the first date of MM frontline treatment for all cohorts to mitigate lead-time bias and implemented a 6-month landmark analysis. To address confounding factors, we applied inverse probability of treatment weighting to adjust for difference in age, sex, comorbidities, and treatment intensity. 
 

 

Results:

Patients who progressed from MGUS to symMM were older (median 71.0 years vs. 66.0 vs. 67.0, p< 0.001) with more comorbidities, particularly renal disease (40.9% vs. 14.5% vs. 21.4%, p< 0.001). Treatment patterns differed, with the smolMM to symMM cohort receiving more doublet regimens as frontline, especially bortezomib-dexamethasone (26.8% vs. 19.5% vs. 13.4%, p< 0.001) .
The 10-year cumulative incidence of progression was 7.8% (95% CI, 6.6-9.1) for MGUS and 36.2% (95% CI, 33.4-39.0) for smolMM, with median times to progression of 3.7 and 2.0 years. After adjustment for demographics, comorbidities, and treatment patterns, both the MGUS to symMM cohort and smolMM to symMM cohort demonstrated significantly improved overall survival compared to the de novo symMM cohort (HR=0.57, 95% CI, 0.43-0.76, p< 0.001; HR=0.83, 95% CI, 0.70–0.97, p=0.023). Median overall survival was 7.9 years (95% CI, 6.0-not reached) for MGUS to symMM cohort, 5.5 years (95% CI, 4.8-7.5) for smolMM to symMM cohort, and 4.4 years (95% CI, 4.3-4.5) for de novo symMM cohort.
 

 

Conclusions:

This population-based analysis underscores the importance of structured surveillance in precursor MM conditions. By identifying and monitoring high-risk individuals, clinicians may be better positioned to intervene earlier in the disease course, ultimately improving survival outcomes in MM.