Correlation of Agent Orange exposure, cytogenetics, and clinical outcomes in multiple myeloma and MGUS.

person Pruthali Kulkarni Baylor Scott & White Health, Temple, TX info_outline Pruthali Kulkarni, Laurel Copeland, James Andy Hall, Jyothi Dodlapati

Authors person Pruthali Kulkarni Baylor Scott & White Health, Temple, TX info_outline Pruthali Kulkarni, Laurel Copeland, James Andy Hall, Jyothi Dodlapati Organizations Baylor Scott & White Health, Temple, TX, Veterans Affairs, Temple, TX, Central Texas Veteran Affairs Hosp, Georgetown, TX Abstract Disclosures Research Funding No funding received None Background: Multiple myeloma (MM) accounts for 1-2% of cancers worldwide. MM and monoclonal gammopathy of unknown significance (MGUS) are associated with Agent Orange exposure (AO) in Vietnam war veterans. Studies show poor outcomes in AO-exposed patients developing MM. No study has evaluated AO exposure and adverse cytogenetics in patients with MM. Methods: We reviewed patients with MGUS and/or MM in the Central Texas Veterans Health Administration system in 2010-2015 to evaluate AO exposure, adverse cytogenetics, transformation from MM to MGUS, and overall survival (OS). Inclusion criteria were active-duty military when AO was used (1961-1971). Presence of 17p13, t(4;14), t(14;16), t(14;20), or Gain 1q by FISH defined high-risk cytogenetics. Poor prognosis per serum free kappa/lambda ratio was defined as < .03 or > 32 K/L (high-risk). Regulatory review approval was obtained. Cox survival models generated hazard rate ratios and their 95% confidence intervals (HR) for AO status (AO, non-AO, undetermined), age, race/ethnicity, transformation, and FISH data. Results: Among 129 veterans, 30% were Black and 12% Hispanic (mean age 74.0 years, SD 6.9, range 59-97). MGUS was diagnosed in 44%, MM 74%, and transformation 19%. FISH abnormalities were rare thus AO association cannot be definitively stated; see table. A subsample with known AO and K/L (n = 81) showed no association: 69% high-risk had AO vs 76% moderate-risk; chi2 = 0.54; p = .46. In the adjusted model, Hispanic patients (HR = 3.3; 1.2-9.1) and those with high-risk cytogenetics (HR = 6.0; 1.1-34.1) had higher mortality; AO was unrelated. Conclusions: Although preliminary analyses find no associations of AO and transformation with OS, ethnicity and FISH abnormality associations are intriguing. Chart review is 50% complete. The paucity of cytogenetics data begs further examination, and continued study is merited to fully recognize what predisposes MM development following AO exposure. Vietnam Veterans AO-exposed (n = 72) Non-AO (n = 22) Undetermined AO (n = 33) Hispanic 11 (16%) 0 (0%) 4 (13%) MGUS 22 (31%) 8 (36%) 3 (9%) MM 36 (50%) 8 (36%) 27 (82%) MGUS+MM 14 (19%) 6 (27%) 3 (9%) High-risk cytogenetics 3 (4%) 1 (5%) 2 (6%) High-risk K/L ratio 20 (28%) 9 (41%) 7 (21%)