Real world analysis of MGUS: Risk of progression and overall survival.

Abstract

e19576 Background: MGUS is a premalignant condition for plasma cell malignancies (PCM) such as multiple myeloma (MM) and lymphoproliferative disorders (LPDs). This real world (RW) study evaluates the long term outcomes in MGUS patients compared to a matched non-MGUS cohort. Methods: The study was conducted using TriNetX, a global RW healthcare database. MGUS pts (n= 148,452) aged ≥18 yrs with an MGUS ICD-10 diagnosis (dx) code (D47.2) with no dx codes for MM or LPDs prior to 6 months after MGUS dx were included. Pts who received prior treatment for MM or LPDs were excluded. The non-MGUS control cohort (n=1,673,702) had no dx of MGUS, or MM, or LPDs prior to index visit, and pts were propensity score-matched by age, sex, and race, resulting in 149,661 pts in each group. Differences in cohort sizes were due to database updates at different query times. Primary outcomes assessed were overall survival (OS) and risk of progression(PGN) to any LPD (ICD-10 codes C81, 82, 83, 84, 85, 86, 88, 90, D47.Z, E85.81), or PCMs (MM-ICD-10: C90 and AL amyloidosis- E85.81) without considering competing risk of death. Survival analyses were conducted using Kaplan-Meier method with log rank comparison. Cox proportional hazards model was used for multivariable analysis to compute hazard ratios (HR). All analyses were conducted using the online TriNetX platform. Results: The mean age at dx in the MGUS cohort was 75 (12) yrs and 51% pts were female. The risk of PGN to PCD was 11.3 % at 10 years and 19.5% at 20 yrs while the risks of PGN to LPD were 15.5% and 26.6% respectively. 10-yr and 20-yr OS rates were-65.2% and 38.2% respectively. In a multivariable model, male sex (HR- 1.25, CI 1.18-1.31), African American race (HR: 1.30, CI 1.23-1.38), monoclonal protein level (HR: 1.13, CI 1.10-1.15) and abnormal free light chain ratio (HR: 1.72, CI 1.45-2.04) were associated with PGN to PCM while higher hemoglobin (HR: 0.95, CI 0.94-0.97) and platelet count (HR: 0.99, CI 0.99-1.0) were inversely associated. A similar association was seen with PGN to LPDs. In the propensity matched cohorts, the characteristics after matching and the estimated risk of PGN to PCMs & LPDs and OS is shown in Table. Median follow up was 2.6 yrs (IQR- 4.8) and 3.1 yrs (IQR- 3.6) in two cohorts. Conclusions: In this large RW study, MGUS was associated with a significantly increased risk of progression to PCMs and LPDs and a reduction in OS. Our findings support established risk factors for progression while identifying potential new predictors. These results highlight the importance of long-term monitoring and individualized risk stratification in MGUS pts. Characteristic MGUS (n= 149,661) Non-MGUS (n=149,661) P-value Age (mean+/- SD) 69 ± 12.7 yrs 69 ± 12.7 yrs 0.741 Female vs male (%) 50.7 vs 44.8 50.7 vs 44.8 0.991 White race (%) 64.0 64.0 0.984 African American race (%) 17.5 17.5 0.966 Overall survival- 20 yr (%) 38.2 59.0 <0.001 PCM-10 yr (%) 11.4 0.4 <0.001 PCM-20 yr (%) 20.1 0.5 <0.001 LPD-10 yr (%) 15.4 1.9 <0.001 LPD-20 yr (%) 26.9 2.3 <0.001