Racial differences in the association between agent orange exposure and the progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US Veterans.

10555 Background: Agent Orange (AO), an herbicide used during the Vietnam War Era (1/9/1962-5/7/1975), is implicated in myelomagenesis due to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD has a long half-life (3.2 years) and many occupations (e.g. pest control, agricultural, etc) are exposed. Work from our group (Liu L, et al., JHO 2024) demonstrated that AO exposure during the high TCDD period of 1/9/1962-11/30/1965 was associated with increased risk of monoclonal gammopathy of undetermined significance (MGUS) to myeloma (MM) progression. Given the higher incidence of MM in Black patients, we assessed whether there are racial differences in this association. Methods: We identified patients diagnosed with MGUS from 10/1/1999-12/31/2021 in the Veterans Health Administration. a published natural language processing-based algorithm was used to confirm diagnoses of MGUS and MM. We excluded: progression<1y, non-IgG/IgA subtype, race other than Black or White due to low numbers, no service during 1/9/1962-5/7/1975, and birth years outside of 1924-1953 so that the groups with and without exposures both have the same birth year range. Patients were stratified by race (Black or White). AO exposure was stratified by three TCDD levels: high (1/9/1962–11/30/1965), medium (12/1/1965–12/31/1970), or low (1/1/1971–5/7/1975). The association between AO exposure levels and progression were estimated using multivariable Fine-Gray subdistribution hazard model with death as a competing event and presented by multivariable-adjusted hazard ratio (aHR). The covariates included age, sex, body mass index (BMI), monoclonal protein (M-protein) level, MGUS subtype, and Charlson Comorbidity Index (CCI). Results: We identified 3,960 Black patients (AO exposed: n=865 [21.8%]) and 6,887 White patients (AO exposed: n=1,986 [28.8%]) with MGUS. Compared to no exposure: Black patients had aHR 1.03 (95% CI 0.51-2.06) for high, aHR 0.88 (95% CI 0.65-1.17) for medium, and aHR 0.3 (0.08-1.18) for low exposure, and White patients had aHR 1.80 (95% CI 1.14-2.83) for high, aHR 1.18 (95% CI 0.95-1.46) for medium, and aHR 1.17 (95% CI 0.66-2.05) for low exposure. Conclusions: White patients had an 80% increased risk of progression with AO exposure during the high TCDD period. No association was observed in Black patients. Multivariable analysis of the association between AO exposure and risk of progression to MM by race. Black (N=3,960) White (N=6,887) Variable aHR (95% CI) P-value aHR (95% CI) P-value AO Exposure No exposure ref. ref. Low TCDD Level 0.30 (0.08-1.18) 0.08 1.17 (0.66-2.05) 0.59 Medium TCDD Level 0.88 (0.65-1.17) 0.37 1.18 (0.95-1.46) 0.14 High TCDD Level 1.03 (0.51-2.06) 0.94 1.80 (1.14-2.83) 0.01 The covariates included age, sex, MGUS subtype, BMI, m-protein, and CCI at MGUS diagnosis.