Race-dependent differences in risk, genomics and Epstein-Barr virus exposure in monoclonal gammopathies: Results of SWOG S0120.

PURPOSE: Risk of myeloma (MM) is increased in African American (AA) populations compared to European American (EA) cohorts. Current estimates of risk of progression of monoclonal gammopathy of undetermined significance (MGUS) are based largely on studies in EA cohorts. Prospective analyses of this risk in AA cohorts are lacking.

PATIENTS AND METHODS: Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120).

RESULTS: Of 331 eligible patients, 57 (17%) were of AA descent. The risk of transformation to clinical malignancy in AA patients was significantly lower than in non-AA cohort (2 year risk 5% vs 15%; 5 year risk 13% versus 24%; log rank p=0.047). Differences in risk were evident for both MGUS and AMM. Gene expression profile (GEP) of CD138-purified plasma cells revealed that all molecular MM subsets can be identified in both cohorts. However the proportion of patients with high risk GEP risk score (GEP-70 gene risk > -0.26) was lower in the AA cohort (0% versus 33%, p=0.01). AA cohorts also have higher levels of antibodies against Epstein-Barr nuclear antigen-1 (EBNA-1; p<0.001).

CONCLUSIONS: These data provide the first prospective evidence that MM precursor states in AA patients may have lower risk disease compared to non-AA counterparts with lower incidence of high-risk GEP and increased EBV seropositivity. Race-dependent differences in biology and clinical risk of gammopathy may impact optimal management of these patients.

TRIAL REGISTRATION: NCT00900263.