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Agent Orange Exposure, Transformation From MGUS to Multiple Myeloma, and Outcomes in Veterans
Jyothi Dodlapati1,2, James A Hall1,2, Pruthali Kulkarni1,2
1Central Texas Veterans Health Care System, Temple.
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.
Insights
Agent Orange exposure did not significantly alter multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS) progression in veterans. However, Agent Orange exposure was linked to reduced mortality for both conditions, while modifiable factors impacted outcomes.
Area of Science:
- Environmental Health
- Oncology
- Epidemiology
Background:
- Multiple myeloma (MM) is a significant cancer affecting 1-2% of all cancer cases.
- Agent Orange (AO) exposure is a known risk factor for monoclonal gammopathy of undetermined significance (MGUS) and subsequent MM development in Vietnam veterans.
Purpose of the Study:
- To investigate survival variations linked to Agent Orange (AO) exposure.
- To analyze the transformation rate from MGUS to MM in relation to AO exposure.
- To identify covariates influencing survival in veterans with MM or MGUS.
Main Methods:
- Utilized Veterans Health Administration (VHA) data to identify Vietnam War veterans with MM or MGUS.
- Employed Cox proportional hazards models to assess survival based on AO exposure and various covariates.
- Defined autologous hematopoietic cell transplantation for MM using procedure codes.
Main Results:
- No significant difference in MGUS to MM transformation rates was observed between AO-exposed and non-exposed groups.
- Agent Orange exposure was associated with slightly lower mortality rates in both MM and MGUS patients.
- Modifiable risk factors like alcohol use disorder and nicotine dependence increased mortality, while factors like Black race, female sex, and transplantation were protective.
Conclusions:
- Focus on modifiable risk factors (nicotine dependence, alcohol/drug use disorders, comorbidities) is crucial, as AO exposure is nonmodifiable.
- Future research should explore the interplay of AO exposure, cytogenetics, and clinical outcomes for optimized veteran care.
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