(PA-347) SECURE Study: Early Findings Suggest MGUS Diagnosis Does Not Increase Psychological Distress

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder found in 3.2% of individuals aged over 50. While its progression to multiple myeloma occurs at ~1% per year, management and follow-up of MGUS in the UK remain inconsistent. With increasing interest in screening, understanding the psychological impact of diagnosis is essential. This interim analysis from SECURE, a national prospective observational cohort, investigates risk stratification and psychological outcomes in individuals with incidentally detected MGUS.


Methods:

SECURE is recruiting 2,000 incidentally diagnosed MGUS patients across 30+ NHS sites from Sept 2023 to Dec 2025, with 60-month follow-up. Annual assessments include validated measures of psychological wellbeing: PHQ-9 (depression), GAD-7 (anxiety), HAI (health anxiety), and IUS-27 (intolerance of uncertainty). Risk stratification is based on M-protein concentration, immunoglobulin isotype, and serum free light-chain (FLC) ratios. Outcomes are compared against 2021 UK Office for National Statistics (ONS) data.


Results:

As of May 2025, 687 participants were enrolled across 29 UK sites. Among 317 risk-stratified individuals (median age 71; 52.4% male; 87.1% White), 27.1% were low risk, 46.7% low-intermediate, 24.0% high-intermediate, and 2.2% high risk of progression. Overall, 52.7% had a pathological FLC ratio, 31.5% had non-IgG MGUS, and 17.0% had M-protein ³ 15 g/L.

PHQ-9 data (n = 432) showed 14.6% (95% CI [11.3, 17.9]) had moderate to severe depressive symptoms, aligning with the ONS figure of 16% (95% CI [15, 18]). GAD-7 results (n = 411) indicated moderate to severe anxiety in 10.7% (95% CI [7.7, 13.7]), slightly below the ONS estimate of 16% (95% CI [14, 18]).

Age-stratified analysis revealed greater psychological burden among younger participants. In those aged 50-69, 21.3% reported moderate/severe depression (ONS: 15%) and 14.6% reported moderate/severe anxiety (ONS: 13%). In contrast, participants aged 70+ had lower rates: 8.9% for depression (ONS: 10%) and 7.3% for anxiety (ONS: 5%).

Health-related anxiety (HAI, n = 416) was predominantly low (80.3%), with only 1.4% classified as high. IUS-27 scores (n = 401) had a mean of 48.1 (SD 20.1) and median of 41.0 on a 27 to 135 scale, where higher scores reflect greater intolerance to uncertainty.


Conclusions:

These interim findings suggest that individuals with incidentally diagnosed MGUS experience rates of depression and anxiety comparable to or lower than the general population. Psychological impact appears age-dependent, with younger participants reporting more symptoms. The overall low burden supports the feasibility of MGUS screening strategies. For those with moderate to severe symptoms, referral to mental health services may be appropriate. The use of HAI and IUS-27 offers novel insight into post-diagnosis experience and may inform tailored support.