Computational Model of Progression to Multiple Myeloma Identifies Optimum Screening Strategies

Abstract

Purpose Recent advances have uncovered therapeutic interventions that might reduce the risk of progression of premalignant diagnoses, such as monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). It remains unclear how to best screen populations at risk and how to evaluate the ability of these interventions to reduce disease prevalence and mortality at the population level. To address these questions, we developed a computational modeling framework. Materials and Methods We used individual-based computational modeling of MGUS incidence and progression across a population of diverse individuals to determine best screening strategies in terms of screening start, intervals, and risk-group specificity. Inputs were life tables, MGUS incidence, and baseline MM survival. We measured MM-specific mortality and MM prevalence after MGUS detection from simulations and mathematic modeling predictions. Results Our framework is applicable to a wide spectrum of screening and intervention scenarios, including variation of the baseline MGUS to MM progression rate and evolving MGUS, in which progression increases over time. Given the currently available point estimate of progression risk reduction to 61% risk, starting screening at age 55 years and performing follow-up screening every 6 years reduced total MM prevalence by 19%. The same reduction could be achieved with starting screening at age 65 years and performing follow-up screening every 2 years. A 40% progression risk reduction per patient with MGUS per year would reduce MM-specific mortality by 40%. Specifically, screening onset age and screening frequency can change disease prevalence, and progression risk reduction changes both prevalence and disease-specific mortality. Screening would generally be favorable in high-risk individuals. Conclusion Screening efforts should focus on specifically identified groups with high lifetime risk of MGUS, for which screening benefits can be significant. Screening low-risk individuals with MGUS would require improved preventions.