Effect of Exposure to Agent Orange (AO) on the Risk of Monoclonal Gammopathy and Subsequent Transformation to Multiple Myeloma (MM): A Single Center Experience from VA Hospital, Detroit

Abstract Background Monocloncal gammopathy of undermined significance (MGUS) is an indolent, pre-malignant plasma cell disorder with the potential of transforming into symptomatic multiple myeloma. There are multiple risk factors contributing to transformation. Agent Orange (AO) has been linked with multiple malignant and non-malignant conditions. Patient and methods We conducted a retrospective chart review of patients with monoclonal gammopathy who were seen at John D. Dingell Veterans Affairs Medical Center (Detroit, MI) between 2005 and 2015 with MGUS, SMM and MM. We explored baseline patient characteristics and explored AO exposure. Dates of diagnosis, dates of progression and expiration dates were recorded to time to progression and overall survival. Results We identified 211 patients with monoclonal gammopathy; 96% were male and 122 were African-American. 11 patients had reported AO exposure. Cumulative risk of progression in the overall population was 1.4% at 1 year. Risk of transformation in the population exposed to AO was significant higher with a HR of 11.19 (95% CI, 2.10 to 59.47; p=0.005). Overall survival was numerically shorter in AO exposed patients with a median OS of 7 yrs. as compared to 11.1 in those not exposed. However, AO exposure was not associated with OS on multivariable analysis (HR, 0.50; 95% CI, 0.07 to 3.83; p=0.508) Conclusions Monoclonal gammopathy is a premalignant condition with the risk of progressing to MM. Exposure to AO has been implicated in multiple conditions including MM. Our study demonstrates an increased risk of progression in patients exposed.