Abstract

Abstract Introduction: Monoclonal gammopathy of unknown significance (MGUS) is a premalignant disorder preceding multiple myeloma that is present in 2.4% of the general population ages 50 years or older. MGUS can be categorized into conventional MGUS that includes IgM MGUS and non-IgM MGUS, and light chain MGUS (defined as those with abnormal free light chain ratio with complete lack of immunoglobulin heavy chain expression on immunofixation). Our objective was to investigate the prognosis of MGUS patients by clinical subgroup and risk stratification suggested by Mayo Clinic. Methods: Data is obtained from National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2004, a nationally representative health survey with follow-up mortality data updated in December 2011. Subjects who were diagnosed with MGUS were included in the study. They were divided into three groups; IgM MGUS, non-IgM MGUS, and light chain MGUS (LC-MGUS). Median overall survival of three groups was obtained using log-rank test and age-adjusted hazard ratio for death between the groups was obtained using cox-proportional regression model. Finally, we also analyzed median survival and age adjusted hazard ratio on conventional MGUS subjects by Mayo clinic MGUS risk stratification based on risk factors of M-protein>1.5g/dL, non-IgG MGUS, and abnormal free light chain (FLC) ratio. Analyses were performed in R software version 3.2.2, and a P-value <0.05 was considered statistically significant. Results: 22,523 subjects in the cohort were screened for MGUS with serum protein electrophoresis, serum protein immunofixation, serum FLC assay, and M-protein typing. There were 483 subjects with MGUS (47 IgM-MGUS, 385 non-IgM MGUS, and 51 LC-MGUS). The median ages of total MGUS subjects, and subgroups were 70, 72.3, 69 and 73 years old, respectively. Median follow-up was 116 months. Median overall survival was 117 months for IgM MGUS, 173 months for non-IgM MGUS, and 109 months for LC-MGUS (p = 0.03). However, the age adjusted hazard ratio (aHR) did not show significant difference between the sub-groups. Likewise, median overall survival of Mayo Clinic MGUS risk group 0, 1, 2 and 3 was 185 months, 163 months, 137 months, and 76.5 months, respectively (p <0.001). Only high-risk group (risk of 3) showed statistically significant aHR 2.9 (95%CI 1.5∼5.6) compared with low risk group (risk of 0). Conclusion: There was no statistically significant mortality difference between MGUS subgroup. Only high-risk group defined by the Mayo Clinic MGUS risk stratification showed inferior survival and higher risk of death compared to rest of MGUS subjects. Further prospective studies are needed to validate our findings and to investigate whether early interventions for MGUS patients by clinical subgroup and risk stratification are needed rather than the current standard management of watchful-waiting. Citation Format: Hyun-Seok Kim, Jieqi Liu, Brittany L. Gladney, Neil Kothari, Noa Biran, Victor Chang, David S. Siegel. Survival prognosis of MGUS patients by clinical and risk subgroup: a result from a nationally representative prospective cohort. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2639.

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