Understanding high-risk smoldering multiple myeloma

Smoldering multiple myeloma (SMM) is an asymptomatic condition with heterogeneous biology and various risks of progression to symptomatic disease. The best-known risk stratification models are Mayo-2018, and IWWG based on tumor burden. Recently, the personalized risk assessment tool PANGEA was introduced. New markers of SMM progression, including genomic and immune characteristics of plasma cells (PCs) and tumor microenvironment, are under investigation, and some have been incorporated into traditional scoring systems. Only one phase 3 clinical trial demonstrated an overall survival benefit of lenalidomide for high-risk SMM patients. The study has limitations, and most guidelines recommend observation or participation in clinical trials for high-risk SMM. High-intensity time-limited treatment strategies for high-risk SMM demonstrated deep responses in single-arm studies. But these treatments can cause adverse effects in asymptomatic patients.This review aims to understand better the risk of SMM progression from a clinical and biological point of view.