Patterns of Monoclonal Immunoglobulins and Serum Free Light Chains Are Significantly Different in African-American Compared to Caucasian MGUS Patients.

Monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma (MM), is 2- to 3-fold more common in African-Americans (AA) than Caucasians (CA). Prior studies have reported clinical features of MGUS and MM to be different among AA compared to CA. Recent studies on CA MGUS cases have found serum free kappa and lambda light chain assays (sFLC) to be highly predictive of MM progression. We have conducted the first study designed to evaluate patterns of sFLC markers in AA.

All AA MGUS patients seen at Walter Reed Army Medical Center (WR) and the Washington DC Veteran's Affairs Medical Center (VA) 2005-2009 were eligible. WR patients were enrolled through a retrospective chart review as sFLC has been performed routinely on MGUS patients. VA patients were enrolled in a prospective trial and sFLC was performed at WR. All patients were categorized for their risk of progression using the Mayo Clinic model (Rajkumar SV Blood 2005) and compared to the Caucasian Mayo Clinic population by the Fisher's exact test (2-tailed).

Eighty-six patients were enrolled, the median age was 73 yrs (42-92) and 74% were male. The MGUS isotype was 87% IgG, 10% IgA, 2% IgM and 1% biclonal. Kappa and lambda light chain disorders were present in 61% and 38%, respectively. The median monoclonal Ig concentration was 0.56 gm/dL (trace-2.33), 47% had a concentration '0.5 g/dL, 30% 0.51-1.0, 20% 1-2 g/dL, and 2% 2-3 g/dL. An abnormal sFLC ratio was present in 49% of patients. Based on the Mayo Clinic model, the risk of progression was: low 42% (95%CI 32-52), low-intermediate 49% (39-59), high-intermediate 8% (4-16) and high 1% (0-7). In comparing our data to the Mayo Clinic data, AA have significantly different distributions of MGUS isotype (p =0.001), lower monoclonal Ig concentration (p=0.0005), presence of an abnormal sFLC ratio (p=0.004) and distributions of Mayo Clinic risk groups (p=0.008) (see table).

The clinical and laboratory features of AA patients with MGUS are distinctly different than in Caucasians, in particular a lower proportion of IgM MGUS, lower monoclonal Ig levels, a higher proportion of abnormal sFLC ratios, and fewer higher-risk patients. IgM MGUS is the precursor to Waldenstrom's macroglobulinemia (WM) and the lower proportion of IgM MGUS in AA is consistent with the very low rate of WM in AA. Non-IgM MGUS should be considered a separate entity and a direct comparison of AA and CA non-IgM MGUS patients using the Mayo Clinic data is planned. The significance of these differences on the risk of malignant progression will require prospective studies in racially diverse populations.

Weiss:The Binding Site, Inc.: Research Funding.