The impact of M-component type and immunoglobulin concentration on the risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance.

BACKGROUND AND OBJECTIVES In this study the impact of gender, age, type of M-component and concentration of immunoglobulins on the risk of malignant transformation in monoclonal gammopathy of undetermined significance (MGUS) was assessed. DESIGN AND METHODS We identified 1,247 cases of MGUS in the period 1978 to 1993 in North Jutland County, Denmark. Data on cancer occurrence in the MGUS cohort were obtained from the Danish Cancer Registry. The expected numbers of incident cancer cases were calculated from age-, sex-, county-, and period-specific cancer incidence rates. The impact of the variables mentioned above on the risk of malignant transformation was analyzed in Poisson regression models. RESULTS The relative risk of IgA compared to IgG was 1.8 (95% confidence interval, 1.1-3.0), while the relative risk of IgM compared to IgG was 1.1 (0.7-1.9). For all three types of MGUS, the risk of malignant transformation was higher among females than among males, and the risk increased with increasing concentration of immunoglobulin with very high risks for the patients with the highest levels of immunoglobulin. Hypogammaglobulinemia was associated with malignant transformation in patients with IgG type MGUS. For IgG and IgM MGUS, the risk decreased with increasing age and with follow-up beyond one year. INTERPRETATION AND CONCLUSIONS Female sex, IgA M-component type and high concentration of the immunoglobulin comprising the M-component were associated with a high risk of malignant transformation. Hypogammaglobulinemia, young age at diagnosis and short follow-up were risk factors in particular for those with IgG MGUS.