Agent Orange Exposure, Transformation From MGUS to Multiple Myeloma, and Outcomes in Veterans

Jyothi Dodlapati; James A Hall; Pruthali Kulkarni; Kelsey B Reely; Amit A Nangrani; Laurel A Copeland

doi:10.12788/fp.0303

Agent Orange Exposure, Transformation From MGUS to Multiple Myeloma, and Outcomes in Veterans

Fed Pract. 2022 Aug;39(Suppl 3):S23-S29a. doi: 10.12788/fp.0303. Epub 2022 Aug 15.

Authors

Jyothi Dodlapati^{1

2}, James A Hall^{1

2}, Pruthali Kulkarni^{1

2}, Kelsey B Reely^{1

2}, Amit A Nangrani², Laurel A Copeland^{3

4}

Affiliations

¹ Central Texas Veterans Health Care System, Temple.
² Baylor Scott and White Health, Temple, Texas.
³ Veterans Affairs Central Western Massachusetts Healthcare System, Leeds.
⁴ University of Massachusetts Chan Medical School, Worcester.

Abstract

Background: Multiple myeloma (MM) accounts for 1% to 2% of all cancers. Exposure to the pesticide Agent Orange (AO) has been established as a potential risk factor for the development of monoclonal gammopathy of undetermined significance (MGUS) and, subsequently, MM in Vietnam War veterans.

Methods: This study explored variation in survival related to AO exposure, transformation from MGUS to MM, and covariates. Vietnam War veterans with MM or MGUS were identified in Veterans Health Administration (VHA) health records data. Cox proportional hazards models analyzed survival as a function of AO, race, ethnicity, body mass index, nicotine dependence, alcohol use disorder, Charlson Comorbidity Index, and treatment. Autologous hematopoietic cell transplantation for MM was defined by procedure codes.

Results: In the VHA 16,366 patients were identified: 11,112 patients diagnosed with MGUS and 7261 with MM during fiscal years 2010 to 2015 were identified; 12% (n = 2007) had both diagnoses. No statistically significant difference in the rate of transformation from MGUS to MM in the AO exposed and AO not exposed groups was found. In survival models, AO exposure was associated with slightly lower mortality. Alcohol use disorder, nicotine dependence, older age, and greater comorbidity burden increased mortality risk. Black race, female sex, obesity/overweight, and hematopoietic cell transplantation for patients with MM were protective factors. AO exposure was associated with decreased mortality for both MM/MGUS groups. Transformation increased mortality risk for patients with MGUS and decreased mortality risk for patients with MM.

Conclusions: Because AO exposure is a nonmodifiable risk factor, focus should be placed on modifiable risk factors (eg, nicotine dependence, alcohol and drug use disorders, underlying comorbid conditions) as these were associated with worse outcomes. Future studies should examine the correlation of AO exposure, cytogenetics, and clinical outcomes in these veterans to best identify their disease course and optimize their care in the latter part of their life.