Race-Dependent Differences in Risk, Genomics, and Epstein-Barr Virus Exposure in Monoclonal Gammopathies: Results of SWOG S0120

Abstract

Purpose: Risk of multiple myeloma is increased in African American (AA) populations compared with 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% vs. 24%; log-rank P = 0.047). Differences in risk were evident for both MGUS and asymptomatic multiple myeloma. Gene expression profile (GEP) of CD138-purified plasma cells revealed that all molecular multiple myeloma 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% vs. 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 multiple myeloma precursor states in AA patients may have lower risk of disease compared with 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: ClinicalTrials.gov NCT00900263.

Figure 1.

Immune and genomic variables by race a. Boxplot of 70-gene risk score (GEP-70) in purified CD138+ tumor cells by race. b. Boxplot of reactivity to Epstein-Barr nuclear antigen-1 (EBNA-1) by race.

Figure 2.

Risk of transformation to clinical MM by race a. Time to development of clinical MM requiring therapy split by AA (n=57) versus other race (n=274). b. Time to development of clinical MM requiring therapy based on diagnosis of MGUS or AMM at study entry.