Clinical and Psychological Outcomes After Monoclonal Gammopathy Screening: A Population-Based Screening Study and Subsequent Randomized Trial of Follow-Up.

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.