In a recent study reported in the Journal of Clinical Oncology, Rognvaldsson et al found that population-based screening for monoclonal gammopathy of undetermined significance (MGUS) led to substantially earlier detection of smoldering multiple myeloma and earlier diagnosis of active multiple myeloma, without evidence of adverse psychological effects.
Study Details
The Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study was designed to evaluate both the clinical benefits and potential harms of population-based screening for monoclonal gammopathies. All residents of Iceland born in 1975 or earlier were invited to participate. A total of 80,759 consented, and 75,422 participants (53% of those invited) underwent screening for monoclonal gammopathy between 2016 and 2020. Among those screened, 3,541 participants were diagnosed with MGUS and randomly assigned to one of three groups: no notification of MGUS status, guideline-based follow-up, or intensified follow-up, which included more extensive bone marrow evaluation. Median follow-up was 4.5 years.
The investigators compared disease progression, diagnostic outcomes, symptom burden, and psychological well-being between participants whose MGUS diagnosis was disclosed and managed (the two intervention arms) and those who remained unaware of their MGUS status (control arm). Psychological outcomes were assessed using Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and life satisfaction questionnaires collected throughout follow-up. More than 11,000 mental health assessments were completed by 2,593 participants, representing 73% of those eligible for psychological analyses.
Key Results
Population screening increased detection of smoldering multiple myeloma by more than 27-fold compared with the control group (8.6% vs 0.3%, hazard ratio [HR] = 27.46, 95% confidence interval [CI] = 10.21–73.86, P < .001). Participants assigned to intensified follow-up were significantly more likely to receive a smoldering multiple myeloma diagnosis than those receiving guideline-based follow-up (HR = 1.65, 95% CI = 1.24–2.19, P < .001), largely because of greater detection among patients with low-risk MGUS. However, rates of active multiple myeloma, multiple myeloma–related malignancies, and symptomatic myeloma did not differ significantly between study groups overall.
Active multiple myeloma and related malignancies were diagnosed approximately 1 year earlier in the intervention groups, with a shorter median time from screening to multiple myeloma diagnosis (2.4 vs 3.8 years, P = .02). Participants aged 40 to 70 years in the intervention groups had a lower risk of active multiple myeloma (HR = 0.56, 95% CI = 0.31–1.00, P = .049). According to the study authors, the mental health assessments revealed that notification of MGUS was not associated with increased depression, anxiety, or life dissatisfaction.
The authors concluded: “These findings demonstrate that population-based screening facilitates earlier detection of [multiple myeloma] and expands access to early intervention without detectable psychological harm.”
Sigurdur Yngvi Kristinsson, MD, PhD, of Faculty of Medicine, University of Iceland, Reykjavik, Iceland, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Black Swan Research Initiative of the International Myeloma Foundation, The European Research Council, and others. For full disclosures of the study authors, visit ascopubs.org.
