Quantifying the contribution of modifiable risk factors for progression of <scp>MGUS</scp> to multiple myeloma in a Veteran population

Multiple myeloma (MM) is the most common plasma cell dyscrasia in the United States with tremendously high burden. MM is preceded by a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS). Although several risk factors for progression have been identified (e.g., older age, male sex, black race, obesity, chemical exposure), their relative contributions remain unclear. Unlike other malignancies, such evidence is lacking for MM despite its high burden. To identify potential intervention strategies that can effectively prevent progression in patients with MGUS, we quantified contributions of the identified modifiable risk factors in the United States Veteran population with MGUS. Compared to the general population, this population is particularly vulnerable to MM as its higher proportions of male and older age as well as the potential prior Agent Orange exposure. We conducted a retrospective cohort study in the Veterans Health Administration and calculated multivariable-adjusted population attributable fractions (aPAFs) of progression accounting for competing risk of death. The aPAF estimates the proportion of progression burden in the population with MGUS that is statistically attributable to a specific risk factor, independent of other factors. In the cohort of 35,073 Veterans with MGUS, among all evaluated risk factors (both modifiable and non-modifiable), excess body mass index (BMI ≥25 kg/m²) was the leading factor (Black: aPAF = 27.1%, 95% CI 19.5%-34.0%; White: 27.2%, 95% CI 20.3%-33.4%; All: aPAF = 27.1%, 95% CI 22.1%-31.9%). Our study highlights the potential of weight management and lifestyle modification for informing the design of targeted MM prevention strategies for Veterans diagnosed with MGUS.