Proposal and validation of prognostic scoring systems for IgG and IgA monoclonal gammopathies of undetermined significance

Purpose:The presenting clinico-hematologic features of1,283 patientswith IgGand IgAmonoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of evolution into multiple myeloma (MM). Experimental Design: Two IgGMGUS populations were evaluated: a training sample (553 patients) and a test sample (378 patients); the IgAMGUS population consisted of 352 patients. Results: Forty-seven of the 553 training group patients and 22 of 378 test group IgG patients developed MMafter a median follow-up of 6.7 and 3.6 years, respectively. Multivariate analysis showed that serum monoclonal component (MC) levels of ≤1.5 g/dL, the absence of light-chain proteinuria and normal serumpolyclonal immunoglobulinlevels defined a prognostically favorable subset of patients, and could be used to stratify the patients into three groups at different10-year risk of evolution (hazard ratio, 1.0, 5.04, 11.2; P < 0.001).This scoring system was validated in the test sample.Thirty of the 352 IgA patients developed MMafter a median follow-up of 4.8 years, and multivariate analysis showed that hemoglobin levels of <12.5 g/dL and reduced serumpolyclonal immunoglobulin correlated with progression. A pooled statistical analysis of all of the patients confirmed the validity ofMayo Clinic riskmodel showing that IgAclass, serumMClevels, and light-chain proteinuria are the most important variables correlated with disease progression. Conclusions: Using simple variables, we validated a prognostic model for IgGMGUS. Among the IgA cases, the possible prognostic role of hemoglobin emerged in addition to a decrease in normal immunoglobulin levels.