Clinical and Psychological Outcomes After Monoclonal Gammopathy Screening: A Population-Based Screening Study and...

Multiple myeloma (MM) and related malignancies develop from an asymptomatic precursor condition, monoclonal gammopathy of undetermined significance (MGUS), detectable via blood testing. The benefits and harms of population-based MGUS screening remain uncertain. We conducted a nationwide screening study for monoclonal gammopathies and a randomized trial of follow-up strategies in Iceland (Iceland Screens, Treats, or Prevents Multiple Myeloma; ClinicalTrials.gov identifier: NCT03327597). In total, 75,422 (53% of those invited) were screened and those with MGUS (n = 3,541) were randomly assigned to no notification (arm 1), guideline-based follow-up (arm 2), or intensified follow-up (arm 3). Progression, symptom burden, and psychological well-being were compared between the control arm (arm 1) and intervention arms (arms 2 and 3). After a median follow-up of 4.5 years, screening led to a 27-fold increase in the detection of smoldering MM (8.6% v 0.3%; hazard ratio, 27.46 [95% CI, 10.21 to 73.86]; P < .001), but active malignancy rates did not differ. Active MM and related malignancy were diagnosed 1 year earlier in the intervention arms with fewer symptomatic presentations and hospitalizations at diagnosis. MGUS notification was not associated with adverse psychological outcomes. These findings demonstrate that population-based screening facilitates earlier detection of MM and expands access to early intervention without detectable psychological harm. Longer follow-up is required to determine the effects on survival and cost-effectiveness.