African-American Patients with Monoclonal Gammopathy Have a Reduced Risk of Transformation to Clinical Myeloma: Results of a Prospective Study SWOG S0120
Authors: Dhodapkar Madhav V , Sexton Rachael , Hoering Antje , Barlogie Bart , Orlowski Robert Z. 
Published: October 2019

Abstract
Introduction:
Both multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with marked racial disparities; incidence of both MM and MGUS is increased nearly 3-fold in African American (AA) compared to Caucasian/European American (EA) cohorts. Current estimates of the risk of progression to clinical malignancy in MGUS and asymptomatic myeloma (AMM) are at 1% and 10% per year respectively, based on data from EA cohorts such as from the Olmstead county in Minnesota. Risk estimates from prospective studies in AA cohorts are urgently needed to guide optimal management of these patients.
Methods:
Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120). All patients underwent uniform staging evaluation at baseline and follow up monitoring for progression to clinical myeloma (CMM). This analysis is focused on the impact of race on clinical and biologic features and risk of progression.
Results:
Of 331 eligible patients, 57 (17%) were of AA descent. Clinical features of the AA cohort were comparable to the non-AA counterparts, with the exception of higher proportion of females (61% versus 43%; p=0.01) and hemoglobin < 12 g/dl (37% versus 23%; p=0.04) in the AA cohort. Among 126 patients with available data on gene expression profile (GEP) of CD138-purified plasma cells, the proportion of patients with GEP-defined subsets was similar between AA and non-AA cohorts. 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 0.04). Differences in risk were evident for both MGUS (2 year risk 0% versus 2 %) and AMM (2 year risk 13% versus 25%). The proportion of patients with high risk GEP signature (GEP-70 gene risk > -0.26) in purified tumor cells was markedly lower in the AA cohort (0% versus 33%, p=0.01). Unbiased analysis of which genes in the AA cohort predict risk of progression is ongoing.
Conclusions:
Together these data provide the first prospective evidence that AA patients with myeloma precursor states carry significantly lower risk of progression to CMM compared to non-AA counterparts. This may be explained in part by the finding that precursor lesions in AA patients have markedly lower proportion of genomic changes (such as GEP70-risk signature derived predominantly from chromosome 1) previously associated with higher risk of malignancy in EA cohorts. The mechanisms underlying the transformation to CMM may therefore differ between AA and EA cohorts, which in turn may impact optimal management of these patients.

Disclosures
Barlogie: Dana Farber Cancer Institute: Other: travel stipend; Celgene: Consultancy, Research Funding; ComtecMed- World Congress on Controversies in Hematology: Other: travel stipend; European School of Haematology- International Conference on Multiple Myeloma: Other: travel stipend; International Workshop on Waldenström's Macroglobulinemia: Other: travel stipend; Millenium: Consultancy, Research Funding; Myeloma Health, LLC: Patents & Royalties: : Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC; Multiple Myeloma Research Foundation: Other: travel stipend. Orlowski:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioTheryX, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Poseida: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Millenium Pharmaceuticals: Consultancy, Research Funding.