Characteristics and clinical course of younger patients with asymptomatic monoclonal gammopathies

Monoclonal gammopathy of undetermined significance (MGUS), smouldering multiple myeloma (SMM) and asymptomatic Waldenström's macroglobulinaemia (aWM) are precursor conditions with variable risk of progression to symptomatic malignancy. We aimed to characterize the asymptomatic monoclonal gammopathies in younger patients among 1237 consecutive patients of which 12.1% were <50 years, while 2% were <40 years. Among patients <50 years, most had MGUS and a female predominance was seen. Of patients <40 years, 71% were females, 50% had SMM and 50% MGUS. Patients <50 progressed with either SLiM criteria (clonal bone marrow plasma cell percentage ≥60% involved:uninvolved serum free light chain ratio ≥100 <1 focal lesions on MRI studies) or bone lesions detected in regular follow-up imaging, without catastrophic complications. For SMM patients <50 years, progression rate to symptomatic disease at 2, 3 and 5 years was 4%, 6% and 12% while for older patients was 9%, 13% and 20%, respectively, but adjusted for baseline risk by 20/2/20, no significant difference emerged. No patient <50 years with MGUS or aWM has yet progressed. Among SMM patients <40 years none was at high risk per 20/2/20, while no progression event occurred after a median follow-up of 3 years. In conclusion, younger patients with asymptomatic monoclonal gammopathies exhibit similar biological features compared to older patients, with generally low progression rates, suggesting early detection and low risk of complications with protocolized follow-up.