Body mass index associated with monoclonal gammopathy of undetermined significance (MGUS) progression in Olmsted County, Minnesota
Geffen Kleinstern, Dirk R. Larson, Cristine Allmer, Aaron D. Norman, Grace Muntifering, Jason P. Sinnwell, Alissa Visram, S. Vincent Rajkumar, Angela Dispenzieri, Robert A. Kyle, Susan L. Slager, Shaji Kumar, Celine M. Vachon
Abstract
Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder that progresses to multiple myeloma (MM), or other plasma-cell or lymphoid disorders at a rate of 1%/year. We evaluate the contribution of body mass index (BMI) to MGUS progression beyond established clinical factors in a population-based study. We identified 594 MGUS through a population-based screening study in Olmsted County, Minnesota, between 1995 and 2003. Follow-up time was calculated from the date of MGUS to last follow-up, death, or progression to MM/another plasma-cell/lymphoid disorder. BMI (kg/m 2 < 25/≥25) was measured close to screening date. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of BMI ≥ 25 versus BMI < 25 with MGUS progression and also evaluated the corresponding c-statistic and 95% CI to describe discrimination of the model for MGUS progression. Median follow-up was 10.5 years (range:0–25), while 465 patients died and 57 progressed and developed MM ( N = 39), AL amyloidosis ( N = 8), lymphoma ( N = 5), or Waldenstrom-macroglobulinemia ( N = 5). In univariate analyses, BMI ≥ 25 (HR = 2.14,CI:1.05–4.36, P = 0.04), non-IgG (HR = 2.84, CI:1.68–4.80, P = 0.0001), high monoclonal (M) protein (HR = 2.57, CI:1.50–4.42, P = 0.001), and abnormal free light chain ratio (FLC r ) (HR = 3.39, CI:1.98–5.82, P < 0.0001) were associated with increased risk of MGUS progression, and were independently associated in a multivariable model (c-statistic = 0.75, CI:0.68–0.82). The BMI association was stronger among females (HR = 3.55, CI:1.06–11.9, P = 0.04) vs. males (HR = 1.39, CI:0.57–3.36, P = 0.47), although the interaction between BMI and sex was not significant ( P = 0.15). In conclusion, high BMI is a prognostic factor for MGUS progression, independent of isotype, M protein, and FLC r . This association may be stronger among females.