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.

Purpose

We 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.

Results

The 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.

Conclusions

Monoclonal 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 1

descriptive statistics on all variables

VariableResponseAll patients/(N=239)
Age N Mean (SD) 239 70.7 (11.7) 
Gender Male 99 ( 41%) 
 Female 140 ( 59%) 
Race Caucasian 108 ( 45%) 
 AA 113 ( 47%) 
 Hispanic 2 ( 1%) 
 Other 16 ( 7%) 
MC type IgG 184 ( 77%) 
 IgA 30 ( 13%) 
 IgM 16 ( 7%) 
 Kappa 3 ( 1%) 
 Lambda 6 ( 3%) 
MC level N Mean (SD) 238 0.7 (0.8) 
No of Ig suppressed 154 ( 64%) 
 57 ( 24%) 
 28 ( 12%) 
IgA suppressed No 207 ( 87%) 
 Yes 32 ( 13%) 
IgG suppressed No 219 ( 92%) 
 Yes 20 ( 8%) 
IgM suppressed No 178 ( 74%) 
 Yes 61 ( 26%) 
Level of suppression >50% 48 (20.1%) 
 <50% 119 (49.8%) 
 None 72 (30.1%) 
M/total N Mean (SD) 229 0.5 (0.5) 
SFLR N Mean (SD) 57 19.0 (73.3) 
UPEP No 119 ( 59%) 
 Yes 82 ( 41%) 
% plasma cells N Mean (SD)Median (Min, Max) 59 4.5 (3.4)4.0 (0.5, 16) 
Hb N Mean (SD) 230 12.4 (2.1) 
Progression No 221 ( 92%) 
 Yes 18 ( 8%) 
VariableResponseAll patients/(N=239)
Age N Mean (SD) 239 70.7 (11.7) 
Gender Male 99 ( 41%) 
 Female 140 ( 59%) 
Race Caucasian 108 ( 45%) 
 AA 113 ( 47%) 
 Hispanic 2 ( 1%) 
 Other 16 ( 7%) 
MC type IgG 184 ( 77%) 
 IgA 30 ( 13%) 
 IgM 16 ( 7%) 
 Kappa 3 ( 1%) 
 Lambda 6 ( 3%) 
MC level N Mean (SD) 238 0.7 (0.8) 
No of Ig suppressed 154 ( 64%) 
 57 ( 24%) 
 28 ( 12%) 
IgA suppressed No 207 ( 87%) 
 Yes 32 ( 13%) 
IgG suppressed No 219 ( 92%) 
 Yes 20 ( 8%) 
IgM suppressed No 178 ( 74%) 
 Yes 61 ( 26%) 
Level of suppression >50% 48 (20.1%) 
 <50% 119 (49.8%) 
 None 72 (30.1%) 
M/total N Mean (SD) 229 0.5 (0.5) 
SFLR N Mean (SD) 57 19.0 (73.3) 
UPEP No 119 ( 59%) 
 Yes 82 ( 41%) 
% plasma cells N Mean (SD)Median (Min, Max) 59 4.5 (3.4)4.0 (0.5, 16) 
Hb N Mean (SD) 230 12.4 (2.1) 
Progression No 221 ( 92%) 
 Yes 18 ( 8%) 
Table 2

Univariate 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-value
Age  70.5 ± 11.9 72.4 ± 8.9 0.663 
Gender Male 91 ( 41%) 8 ( 44%) 0.787 
 Female 130 ( 59%) 10 ( 56%)  
Race Caucasian 96 ( 43%) 12 ( 67%) 0.289 
 AA 108 ( 49%) 5 ( 28%)  
 Hispanic 2 ( 1%) 0 ( 0%)  
 Other 15 ( 7%) 1 ( 6%)  
MC type IgG 170 ( 77%) 14 ( 78%) 0.480 
 IgA 26 ( 12%) 4 ( 22%)  
 IgM 16 ( 7%) 0 ( 0%)  
 Kappa 3 ( 1%) 0 ( 0%)  
 Lambda 6 ( 3%) 0 ( 0%)  
MC level  0.7 ± 0.8 1.4 ± 0.8 <.001 
No of PC suppressed 148 ( 67%) 6 ( 33%) 0.016 
 49 ( 22%) 8 ( 44%)  
 24 ( 11%) 4 ( 22%)  
IgA suppression No 193 ( 87%) 14 ( 78%) 0.252 
 Yes 28 ( 13%) 4 ( 22%)  
IgG suppression No 204 ( 92%) 15 ( 83%) 0.186 
 Yes 17 ( 8%) 3 ( 17%)  
IgM suppression No 169 ( 76%) 9 ( 50%) 0.013 
 Yes 52 ( 24%) 9 ( 50%)  
Level of suppression >50% 40 (18.1%) 8 (44.4%) 0.047 
 <50% 113 (51.1%) 6 (33.3%)  
 None 68 (30.8%) 4 (22.2%)  
M/total  0.5 ± 0.5 0.7 ± 0.2 0.001 
SFLR  18.1 ± 74.7 33.6 ± 45.7 0.033 
UPEP No 108 ( 59%) 11 ( 65%) 0.629 
 Yes 76 ( 41%) 6 ( 35%)  
% plasma cells  3.7 ± 2.9 9.5 ± 1.9 <.001 
Hb  12.4 ± 2.1 11.9 ± 1.9 0.320 
Time to progression  N/A 30 (12, 51)  
VariableResponseNo progression(N= 221)Progression(N= 18)p-value
Age  70.5 ± 11.9 72.4 ± 8.9 0.663 
Gender Male 91 ( 41%) 8 ( 44%) 0.787 
 Female 130 ( 59%) 10 ( 56%)  
Race Caucasian 96 ( 43%) 12 ( 67%) 0.289 
 AA 108 ( 49%) 5 ( 28%)  
 Hispanic 2 ( 1%) 0 ( 0%)  
 Other 15 ( 7%) 1 ( 6%)  
MC type IgG 170 ( 77%) 14 ( 78%) 0.480 
 IgA 26 ( 12%) 4 ( 22%)  
 IgM 16 ( 7%) 0 ( 0%)  
 Kappa 3 ( 1%) 0 ( 0%)  
 Lambda 6 ( 3%) 0 ( 0%)  
MC level  0.7 ± 0.8 1.4 ± 0.8 <.001 
No of PC suppressed 148 ( 67%) 6 ( 33%) 0.016 
 49 ( 22%) 8 ( 44%)  
 24 ( 11%) 4 ( 22%)  
IgA suppression No 193 ( 87%) 14 ( 78%) 0.252 
 Yes 28 ( 13%) 4 ( 22%)  
IgG suppression No 204 ( 92%) 15 ( 83%) 0.186 
 Yes 17 ( 8%) 3 ( 17%)  
IgM suppression No 169 ( 76%) 9 ( 50%) 0.013 
 Yes 52 ( 24%) 9 ( 50%)  
Level of suppression >50% 40 (18.1%) 8 (44.4%) 0.047 
 <50% 113 (51.1%) 6 (33.3%)  
 None 68 (30.8%) 4 (22.2%)  
M/total  0.5 ± 0.5 0.7 ± 0.2 0.001 
SFLR  18.1 ± 74.7 33.6 ± 45.7 0.033 
UPEP No 108 ( 59%) 11 ( 65%) 0.629 
 Yes 76 ( 41%) 6 ( 35%)  
% plasma cells  3.7 ± 2.9 9.5 ± 1.9 <.001 
Hb  12.4 ± 2.1 11.9 ± 1.9 0.320 
Time to progression  N/A 30 (12, 51)  
Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.