A risk-stratification model based on the initial concentration of the serum monoclonal protein and MYD88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders.

IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenstrom macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1-2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8 center dot 5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1 center dot 32% per year (95% confidence interval [CI] 0 center dot 80-2 center dot 20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23 center dot 3, 95% CI 2 center dot 0-273 center dot 3, P = 0 center dot 012 and HR 24 center dot 4, 95% CI 2 center dot 2-275 center dot 3, P = 0 center dot 010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11 center dot 6% at 5 years and 38 center dot 0% at 10 years in MYD88-mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0% at 5 years and 1 center dot 1% at 10 years for patients with none or one risk factor. This risk-stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow-up.