Diagnosis, risk stratification and management of smouldering multiple myeloma

New therapies have markedly improved survival outcomes for patients with multiple myeloma (MM). However, the onset of active disease, as defined by the 2014 International Myeloma Working Group SLiM-CRAB criteria, is often linked to substantial and irreversible morbidity. MM always develops from an asymptomatic precursor state called smouldering multiple myeloma (SMM). The clinical trajectory of SMM varies considerably; low-risk SMM often has an indolent course, similar to monoclonal gammopathy of undetermined significance, whereas nearly half of the subset of patients with high-risk SMM have progression to symptomatic MM within 2 years. Highly active treatments for MM, which remains an incurable disease, are being investigated for the management of SMM, with the aim of delaying or even preventing such progression. Both early therapeutic intervention and active surveillance are reasonable management options for patients with high-risk SMM, with decisions individualized through a detailed risk-benefit discussion with the patient. In this Review, we discuss current approaches for diagnostic evaluation, risk stratification and management of SMM, as well as future challenges and emerging opportunities in the field.