Prognostic Factors for Malignant Transformation in Monoclonal Gammopathy of Undetermined Significance (MGUS): Experience of One Institution

Reviewer: Eric Shinohara MD, MSCI
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 22, 2007

Presenter: Sackmann, F
Presenter's Affiliation: FUNDALEU, Argentina
Type of Session: Scientific

Background

MGUS has a prevalence of 1 to 3%.
MGUS generally has an indolent course, however some patients (pts) will progress to a malignant neoplasm. Identifying prognostic factors that can identify pts who will progress is important.
The purpose of this study was to assess the value of simple hematological or biochemical parameters detected at diagnosis as predictors for malignant transformation.
This study determined the rate of malignant transformation, as well as the endpoints of progression free survival (PFS) and overall survival (OS).

Materials and Methods

This study is a retrospective analysis of 236 pts with MGUS. Pts with MGUS were defined as having less than 3 mg/dl of monoclonal antibody, no bone lesions, and no renal insufficiency. Progression was defined as: when monoclonal antibody increased to greater than 3 mg/dl, bone marrow biopsy revealed greater than 10% plasma cells or lytic bone lesions were found.
PFS and OS were calculated using the Kaplan Meier method and the curves were compared using the log-rank test. The identification of prognostic factors was made using Cox models.

Results

Patients had a median monoclonal component (MC) was 0.6 gm/dl.
Among all pts, the monoclonal component was IgG in 74%, IgA in 17%, IgM in 9% and biclonal in 0.5%. The light chain was Kappa in 61% of the pts. Bence Jones protein was detected in only 12% of pts.
Uninvolved immunoglobulins (UI) were reduced in 20% of the pts. Bone marrow analysis was performed in 64 pts. The median number of plasma cells found in the bone marrow was 4%. The median hemoglobin was 13.3 gm/dl.
Lactic dehydrogenase, albumin, B2microglobulin and erythrocyte sedimentation rate were normal in 97%, 87%, 53% and 42% respectively.
With a median follow up of 58 months (6.2 – 375 months), 17 pts (7%) progressed to a malignancy (15 multiple myeloma, 1 NHL, and 1 amyloidosis). The cumulative probability of transformation to malignant neoplasm was 12% at 10 years. PFS and OS at 10 years 88% and 95%, respectively.
MC concentration (p = 0.04, HR 4.73, CI 1.06 – 21) and reduction of UI (p = 0.01, HR 5.8, CI 1.48 – 22.7) had prognostic value for progression.

Author's Conclusions

MC concentration and UI level at diagnosis identify a subgroup of pts with MGUS who are at higher risk of malignant transformation.
These findings are consistent with findings from previous studies.
Bone marrow biopsy should be performed in patients at high risk.

Clinical/Scientific Implications

The present study confirmed previously described prognostic variables for the malignant transformation of patients with MGUS. They found that MC concentration and low levels of UI were correlated with the risk for malignant transformation.
MC increase and reduction of UI appear to be closely correlated, which may affect the multivariant analysis results. Determining other prognostic variables, which are not closely related, that may contribute to malignant transformation could strengthen the multivariant analysis.
Determining which patients with MGUS are at highest risk for malignant transformation and require the closest surveillance would allow for earlier identification of progression. This study suggests that MC concentration and reduction of UI are of value as prognostic markers. However, as these variables were not selected a priori and the data used was retrospective, prospective studies using these markers as prognostic factors for malignant transformation are needed.