Maria-Victoria Mateos, MD, PhD, of the University of Salamanca, Salamanca, Spain, and Irene Ghobrial, MD, of the Dana-Farber Cancer Institute, Boston, MA, discuss strategies for the management of smoldering myeloma, a precursor stage of multiple myeloma. Dr Mateos explains that patients with smoldering myeloma are stratified based on clinical markers such as the size of the M-protein component, plasma bone marrow infiltration as well as free light-chain (FLC) ratio. Dr Ghobrial talks on the incorporation of markers such as MAP kinase mutations and DNA repair mutations to further refine patient stratification. Additionally, Dr Ghobrial advocates earlier intervention with novel immunotherapies for the treatment of smoldering myeloma to improve progression-free survival outcomes. This interview took place during the 18th International Myeloma Workshop (IMW 2021) congress.