FISH abnormalities in Agent Orange–associated multiple myeloma.

Abstract

e20056 Background: Multiple myeloma (MM) is a plasma cell neoplasm that accounts for approximately 10% of all hematologic malignancies. Molecular investigations have identified a wide heterogeneity in MM at the genomic and epigenomic levels, often with IgH translocations and trisomies seen early in the pathogenesis. Etiological factors, though, are still not well characterized. Agent Orange (AO) was a herbicide widely used as a defoliant by the U.S. military during the Vietnam War. Studies have indicated a probable causative link between exposure to AO and the development of multiple myeloma; in fact, MM is now recognized by the VA as a service-connected diagnosis. However, there have been few small studies addressing whether there are any unique molecular findings in AO associated MM. We sought to determine if there were any specific myeloma FISH abnormalities seen in AO associated MM and if there were any differences in their respective survival. Methods: We included all patients diagnosed with MM from 2010-2022 at Louis Stokes VA Medical Center (Cleveland, OH). Data collected included: age, sex, race, year of diagnosis, AO exposure, bone marrow biopsy results and myeloma FISH panel results. We defined high risk MM based on the presence of t(14;16), t(14;20), del 17p/TP53 or gain 1q. Overall survival (OS) was calculated from date of diagnosis to death. Results: We included 162 patients with MM, among them 32 had AO exposure. There was no significant difference in age or race between exposed and non-exposed patients. MM FISH results were available for 137 patients. Overall, 20% of patients had high risk group cytogenetics and there was no significant difference based on AO exposure. However, there was a trend for increased TP53 mutations in those exposed to AO, although this did not reach statistical significance (8% vs. 3.6%, p = 0.3). Median OS was 72 months for non-exposed patients and 98 months for exposed patients, with no significant difference observed (p = 0.18). Conclusions: In this single institution, retrospective study, AO exposure was not associated with a higher incidence of high-risk cytogenetics by FISH in MM. There was a trend for increased TP53 mutation with AO exposure, but the cohort was small and did not reach statistical significance. In addition, AO exposure was not associated with a worse survival. Further studies are needed to clarify the effects of AO on the development of MM, including genomic and transcriptomic analysis to elucidate the pathobiology of this disease. [Table: see text]