Evaluation of Prognostic Factors for Malignant Transformation of Monoclonal Gammopathy of Undetermined Significance

Background: monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1 to 3%. Although it has an indolent evolution, some patients (pts) will develop a malignant transformation. Thus, prognostic factors that may identify pts who will progress are important. We update our experience published before.

Methods: we performed a retrospective analysis of 387 pts with MGUS diagnosed between 1982 and 2008 in our institution to identify simple haematological variables associated with progression. Actuarial progression free survival (PFS) and overall survival (OS) were also calculated. MGUS was diagnosed when monoclonal component (MC) was present at a concentration of 3 gr per decilitre or less, no or only moderate amounts of monoclonal light chains in the urine, absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to monoclonal protein; and if performed a proportion of plasma cells of 10 percent or less. MC was detected by agarose gel and/or cellulose acetate electrophoresis in serum and/or urine. The identification of the MC was performed by immunoelectrophoresis or immunofixation and the quantification of immunoglobulins, by radial immunodifussion. Progression to myeloma was defined by: MC > 3 gr/dl, plasma cell infiltration > 10%, or associated lytic bone lesions. Progression to another B-cell neoplasm was considered when there was histologic evidence of the disease. The identification of prognostic factors was made using Cox models. PFS and OS were calculated using the Kaplan Meier method and the curves were compared with the log-rank test.

Results: The median (md) age at diagnosis was 62 years (range 24–89 years) and 18% of the pts were younger than 50. Anemia not related to the monoclonal protein was present in 18% of the pts. Albumin, beta 2 microglobulin and erythrocyte sedimentation rate (ESR) were normal in 88%, 50% and 41% of the pts, respectively. MC was 0.6 gr/dl (range 0.1–2.9). In 70% of the cases it was IgG, 15% IgA, 13% IgM and 2% biclonal. The light chain was Kappa in 65% of the pts. Bence Jones was detected in only 9%. Uninvolved immunoglobulins (UI) were reduced in 21% of the pts. Bone marrow analysis were performed in 79 pts (20%) and md plasma cell infiltration was 3 (range 0 – 10). The 387 pts were followed for 2340 person-years (md 4.75 years, range 0 – 31) during which 31 pts (8%) evolved to a malignancy (23 multiple myeloma, 7 NHL, and 1 amyloidosis) and 17 (4.6%) died (3 related to progressive disease, 6 related to non hematological malignancy, 2 associated to cardiovascular disorders, 2 secondary to infection and 4 of unknown cause). PFS and OS at 10 years were 89% and 91%, respectively. The overall risk of progression was 1.3% per year. Among all the variables analysed (age, gender, hemoglobin, albumin, beta 2 microglobulin, ESR, type and concentration of MC, Bence Jones and reduction of UI), only MC concentration (HR 4.81, CI 2.2 – 10.32, p = 0.00007) and ESR (HR 3.67, CI 1.7 – 7.88, p = 0.001) had prognostic value for progression.

Conclusions: MC concentration and ESR at diagnosis identified a subgroup of pts with higher risk of transformation in our experience.