Determining the Clinical Significance of Monoclonal Gammopathy of Undetermined Significance: A SEER-Medicare Population Analysis

The follow-up examination of patients with monoclonal gammopathy of undetermined significance (MGUS) to screen for malignant transformation is a common practice; however, evidence is lacking. Our population-based study has shown that patients with multiple myeloma, Waldenstrom macroglobulinemia, and lymphoplasmacytic lymphoma who had MGUS follow-up examinations 1 year before a cancer diagnosis might have fewer major complications and longer survival compared with those without such follow-up. Background: Clinical guidelines have recommended annual follow-up examinations of most patients with monoclonal gammopathy of undetermined significance (MGUS); however, evidence supporting this practice is lacking. We performed a population-based study to examine the patterns of disease presentation and outcomes of patients with multiple myeloma, Waldenstrom macroglobulinemia, and lymphoplasmacytic lymphoma (monoclonal gammopathy associated malignancies) comparing those with or without a previous MGUS follow-up examination. Materials and Methods: Patients with monoclonal gammopathy-associated malignancy from 1994 through 2007 were identified using the Surveillance, Epidemiology, and End Results Medicare linked database and divided into 2 cohorts: those with follow-up (MGUS follow-up examination preceding the diagnosis) and those with no follow-up (no such follow-up examination). We compared the outcomes, including the rates of major complications at cancer diagnosis (acute kidney injury, cord compression, dialysis use, fracture, and hypercalcemia) and survival using propensity score adjustment and Cox proportional hazard models. All statistical tests were 2-sided. Results: Of the 17,457 study patients, 6% had undergone MGUS follow-up. After multivariable modeling, the follow-up group had significantly fewer major complications at diagnosis (odds ratio 0.68; 95% confidence interval [CI], 0.57-0.80) and better diseasespecific (median, 38 vs. 29 months, P < .001; hazard ratio [HR] 0.85; 95% CI, 0.76-0.94) and overall (median, 23 vs. 19 months, P < .001; HR 0.87; 95% CI, 0.80-0.95) survival. Conclusion: Patients with MGUS follow-up preceding the diagnosis of a monoclonal gammopathy associated malignancy can experience fewer major complications and have longer survival than those without such follow-up examinations. Future studies replicating our findings in the nonMedicare population and determining the optimal schedule and cost-effectiveness of MGUS follow-up are warranted.