Incidence of Monoclonal Gammopathy of Undetermined Significance and Estimation of Duration Before First Clinical Recognition Terry M. Therneau, PhD,

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Incidence of Monoclonal Gammopathy of Undetermined Significance and Estimation of Duration Before First Clinical Recognition Terry M. Therneau, PhD, Robert A. Kyle, MD, L. Joseph Melton, MD, Dirk R. Larson, MS, Joanne T. Benson, BA, Colin L. Colby, BS, Angela Dispenzieri, MD, Shaji Kumar, MD, Jerry A. Katzmann, PhD, James R. Cerhan, MD, PhD, S. Vincent Rajkumar, MD Mayo Clinic Proceedings Volume 87, Issue 11, Pages 1071-1079 (November 2012) DOI: 10.1016/j.mayocp.2012.06.014 Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions

FIGURE 1 Prevalence of monoclonal gammopathy of undetermined significance (MGUS) according to age. Error bars indicate 95% confidence intervals. Ages older than 90 years have been collapsed to 90 years of age. From Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362-1369. © 2006. Massachusetts Medical Society. Reproduced with permission from Massachusetts Medical Society. Mayo Clinic Proceedings 2012 87, 1071-1079DOI: (10.1016/j.mayocp.2012.06.014) Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions

FIGURE 2 Incidence model using the prevalence estimates of monoclonal gammopathy of undetermined significance (MGUS), the rate of MGUS progression to multiple myeloma or related malignant neoplasm (δ2), and the death rates (λ1-λ3) as inputs to calculate the incidence (δ1). Mayo Clinic Proceedings 2012 87, 1071-1079DOI: (10.1016/j.mayocp.2012.06.014) Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions

FIGURE 3 Rate of conversion from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma by the age of the patient. This figure shows the estimated yearly progression of MGUS in patients by current age and M-spike size for a joint fit of men and women. Separate fits of the male and female cohorts were also performed but gave a small increase in the goodness of fit (P=.31). Mayo Clinic Proceedings 2012 87, 1071-1079DOI: (10.1016/j.mayocp.2012.06.014) Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions

FIGURE 4 Estimated incidence of monoclonal gammopathy of undetermined significance by age and sex. The solid line corresponds to a smoothing spline fit and the dashed line to a linear fit with one knot. Mayo Clinic Proceedings 2012 87, 1071-1079DOI: (10.1016/j.mayocp.2012.06.014) Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions

FIGURE 5 Fitted vs observed prevalence of monoclonal gammopathy of undetermined significance per 100,000 population by age and sex. The solid line corresponds to a smoothing spline fit and the dashed line to a linear fit with one knot. Circles represent the observed age- and sex-specific prevalence rates from the prevalence cohort. Mayo Clinic Proceedings 2012 87, 1071-1079DOI: (10.1016/j.mayocp.2012.06.014) Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions

FIGURE 6 Prevalence of monoclonal gammopathy of undetermined significance (MGUS) by population-based testing in Olmsted County, Minnesota, vs clinical detection. Mayo Clinic Proceedings 2012 87, 1071-1079DOI: (10.1016/j.mayocp.2012.06.014) Copyright © 2012 Mayo Foundation for Medical Education and Research Terms and Conditions