Predicting Disease Progression to Multiple Myeloma (MM) From MGUS/SMM In SWOG-0120 Observational Trial

Most MM develops through an asymptomatic precursor stage. Current analyses understanding the risk of progression to clinical MM are based on limited set of variables. In 2002, South West Oncology Group (SWOG) began a prospective observational clinical trial of patients with asymptomatic plasmaproliferative disorders (PCD) to evaluate clinical, imaging, genetic and immunologic features predictive of disease progression.

All patients with asymptomatic PCD underwent detailed staging evaluation at study entry and were prospectively followed at 3–6 month intervals until disease progression requiring therapy. Data from clinical features at baseline were evaluated to assess the risk for progression to clinical MM (P-MM).

Between 11/2002 and 4/2010, 230 patients have been enrolled, of whom 140 were deemed to have smoldering MM (SMM) and 90 monoclonal gammopathy of undetermined significance (MGUS), based on international myeloma working group criteria. The two groups differed in terms of abnormal serum free light chain ratio (FLCR; SMM: 79%, MGUS: 52%; p<0.001) and low levels of uninvolved Ig (SMM: 77%, MGUS; 53%; p<0.001), while no significant differences were noted in the proportion of patients with elevated beta 2 microglobulin (B2M) >=3.5mg/L, albumin <3.5 g/dL, elevated C-reactive protein >8mg/L or lactate dehydrogenase (LDH). Among 13 variables potentially linked to P-MM, baseline B2M >=3.5mg/L, baseline serum albumin <3.5g/dL, serum M-spike and bone marrow plasmacytosis (as continuous variables), serum calcium >8 mg/dL, abnormal FLCR and low levels of uninvolved Ig were all associated with greater propensity of P-MM on univariate analysis. However upon multivariate analysis, abnormal serum FLCR and SMM disease type were the only surviving adverse variables predictive of disease progression.

These data demonstrate in the context of a large prospective multicenter trial that abnormal FLCR is a dominant predictor of clinical malignancy in asymptomatic PCD. These findings support the need to understand the biology of abnormal FLCR and incorporate novel criteria based on imaging, genetics and host response.

No relevant conflicts of interest to declare.