8056 Background: Roughly 37% of Multiple Myeloma (MM) patients in the U.S. are non-white minorities. Advanced stage at diagnosis and specific cytogenetic abnormalities are associated with high-risk disease and poor prognosis. Few studies evaluated these risk factors in ethnic minorities. To further investigate, we analyzed ethnic variations in characteristics and outcomes of high-risk MM patients who were treated at our institution in Fresno, CA (49.6% Hispanic population). Methods: Patients diagnosed with high-risk MM at Community Medical Centers from 1-1-2011 to 12-31-2020 were included. High risk was defined by Mayo Clinic mSMART 3.0 classification. Demographic and disease-relevant information were collected. Cytogenetics, R ISS stage, 1st line treatment (doublet vs triplet), and treatment response (IMWG response criteria) were evaluated. Hispanic and non Hispanic comparisons were made by Fisher’s exact test where appropriate. Progression Free Survival (PFS) and Overall Survival (OS) were evaluated by Kaplan-Meier estimates and compared via log-rank test. Univariate cox proportional hazard model for survival was used to examine the association of variables with mortality risk after 1st line therapy. Results: 147 MM patients were screened. 42 high risk patients were identified: 11 (26%) Hispanic, 31 (74%) non Hispanic (22 white, 8 African American, 1 East Indian). Median age at diagnosis was 65. 26 (61%) were females. 25 (59%) were R ISS stage 3. Hispanic vs non Hispanic median income was $46119 vs $65080 (p=0.035). 6 Hispanics had Medi-Cal insurance vs 2 non-Hispanics (54.6% vs 6.5%, p=0.003). More Hispanics had Lambda light chain disease (73% vs 26%; p=0.01). 13 non Hispanics had del 17p vs 0 Hispanics (p=0.009). 40/42 patients (95%) received triplet therapy. 4 Hispanics received ASCT vs 9 non Hispanics (40% vs 33.3%, p=0.716). Hispanics and non Hispanics did not have significantly different treatment responses per IMWG criteria (p=0.799). No significant difference in PFS was seen between Hispanics and non Hispanics (805 vs 793 days; p=0.089); OS was better in Hispanics (1062 days vs 453 days; p=0.008). Per univariate cox proportional Hazard model, female sex (HR 4.34) and age (HR 1.05) were associated with higher mortality while Hispanic ethnicity was associated with lower mortality (HR 0.19). Conclusions: Hispanic and non Hispanic high risk MM patients differed significantly in median income, insurance, and del 17p incidence. These did not translate to a difference in 1st line therapy or treatment response. OS in our study is higher in Hispanic high-risk MM patients compared to other ethnicities and warrants further investigation. [Table: see text]