A computational model of MGUS progression to Multiple Myeloma identifies optimum screening strategies and their effects on mortality

Abstract

Recent advances uncovered therapeutic interventions that might reduce the risk of progression of premalignant diagnoses, such as from 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. 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 following MGUS detection from simulations and mathematical precition modeling. We showed that 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 progression risk-point estimate of 61% risk, starting screening at age 55 and follow-up screening every 6yrs reduced total MM prevalence by 19%. The same reduction could be achieved with starting age 65 and follow-up every 2yrs. A 40% progression risk reduction per MGUS patient per year would reduce MM-specific mortality by 40%. Generally, age of screening onset and frequency impact disease prevalence, progression risk reduction impacts both prevalence and disease-specific mortality, and screeenign would generally be favorable in high-risk individuals. Screening efforts should focus on specifically identified groups of high lifetime risk of MGUS, for which screening benefits can be significant. Screening low-risk MGUS individuals would require improved preventions.