Polyclonal Gamma Globulin Suppression and Risk Of MGUS Progression Into Multiple Myeloma

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is the most common form of plasma cell dyscrasia, with a prevalence of 3% in the general population above age of fifty. MGUS has a malignant evolution rate of 1% per year. Large longitudinal studies have suggested that virtually all patients diagnosed with multiple myeloma (MM) had a preceding MGUS, with 75 % having detectible Monoclonal (M) protein ≥8 years prior to diagnosis. It is important to identify the features at diagnosis that can predict neoplastic transformation to MM. PurposeWe identified 239 patients at our institute in whom MGUS was diagnosed between 2000 and 2010. The presenting clinico-hematologic features were correlated with the frequency of evolution into MM to identify early predictors of evolution. The primary end point was progression to MM. ResultsThe patients' mean age was 70.7 years. The Male/Female ratio was 0.7. The mean concentration of the M component (MC) was 0.7 g/dL. IgG was the most frequent MC (77%), followed by IgA (13%). The median ratio of MC protein to total protein was 0.5. Single or multiple background polyclonal (PC) suppression was noted in 36% of patients. PC suppression of 50% or more was noted in 20.1% of patients, 49.8% had < 50% and 30.1% had no suppression. Mean bone marrow plasma cell percentage was 4.5 percent and mean hemoglobin was 12.4 g/dL.Eighteen of the 239 patients with MGUS progressed into MM over ten years of follow up.Univariate comparisons of all variables between those who progressed and those who did not, showed that the initial concentration of the serum M protein, ratio of M protein to the total protein, number of PC gamma globulins suppressed, degree of PC suppression and IgM gamma globulin suppression were statistically significant risk factors that correlated with progression into MM. Fourteen out of eighteen patients with progressive disease had either PC suppression or background IgM suppression. ConclusionsMonoclonal protein concentration, ratio of M protein to the total protein and abnormal serum free light chain ratio are simple variables that have been shown in multiple previous studies to predict the progression of MGUS into MM. In our study, we additionally found that number of PC suppressed, degree of suppression and IgM suppression are also key risk factors that can predict progression.We believe that these variables can be potentially applied into an approach that uses a detailed risk stratification system to predict which cases of MGUS will progress into MM and to provide more intensive monitoring for patients more likely to progress.Table 1descriptive statistics on all variablesVariableResponseAll patients/(N=239)AgeN Mean (SD)239 70.7 (11.7)GenderMale99 ( 41%)Female140 ( 59%)RaceCaucasian108 ( 45%)AA113 ( 47%)Hispanic2 ( 1%)Other16 ( 7%)MC typeIgG184 ( 77%)IgA30 ( 13%)IgM16 ( 7%)Kappa3 ( 1%)Lambda6 ( 3%)MC levelN Mean (SD)238 0.7 (0.8)No of Ig suppressed0154 ( 64%)157 ( 24%)228 ( 12%)IgA suppressedNo207 ( 87%)Yes32 ( 13%)IgG suppressedNo219 ( 92%)Yes20 ( 8%)IgM suppressedNo178 ( 74%)Yes61 ( 26%)Level of suppression>50%48 (20.1%)<50%119 (49.8%)None72 (30.1%)M/totalN Mean (SD)229 0.5 (0.5)SFLRN Mean (SD)57 19.0 (73.3)UPEPNo119 ( 59%)Yes82 ( 41%)% plasma cellsN Mean (SD)Median (Min, Max)59 4.5 (3.4)4.0 (0.5, 16)HbN Mean (SD)230 12.4 (2.1)ProgressionNo221 ( 92%)Yes18 ( 8%)Table 2Univariate comparisons of all variables between those who progressed and those who did not. Bold p-value is statistically significant.VariableResponseNo progression(N= 221)Progression(N= 18)p-valueAge70.5 ± 11.972.4 ± 8.90.663GenderMale91 ( 41%)8 ( 44%)0.787Female130 ( 59%)10 ( 56%)RaceCaucasian96 ( 43%)12 ( 67%)0.289AA108 ( 49%)5 ( 28%)Hispanic2 ( 1%)0 ( 0%)Other15 ( 7%)1 ( 6%)MC typeIgG170 ( 77%)14 ( 78%)0.480IgA26 ( 12%)4 ( 22%)IgM16 ( 7%)0 ( 0%)Kappa3 ( 1%)0 ( 0%)Lambda6 ( 3%)0 ( 0%)MC level0.7 ± 0.81.4 ± 0.8<.001No of PC suppressed0148 ( 67%)6 ( 33%)0.016149 ( 22%)8 ( 44%)224 ( 11%)4 ( 22%)IgA suppressionNo193 ( 87%)14 ( 78%)0.252Yes28 ( 13%)4 ( 22%)IgG suppressionNo204 ( 92%)15 ( 83%)0.186Yes17 ( 8%)3 ( 17%)IgM suppressionNo169 ( 76%)9 ( 50%)0.013Yes52 ( 24%)9 ( 50%)Level of suppression>50%40 (18.1%)8 (44.4%)0.047<50%113 (51.1%)6 (33.3%)None68 (30.8%)4 (22.2%)M/total0.5 ± 0.50.7 ± 0.20.001SFLR18.1 ± 74.733.6 ± 45.70.033UPEPNo108 ( 59%)11 ( 65%)0.629Yes76 ( 41%)6 ( 35%)% plasma cells3.7 ± 2.99.5 ± 1.9<.001Hb12.4 ± 2.111.9 ± 1.90.320Time to progressionN/A30 (12, 51) Disclosures:No relevant conflicts of interest to declare.