Next generation sequencing reveals spatio-temporal clonal heterogeneity in an aggressive relapsed/refractory multiple myeloma case

Multiple myeloma (MM) is characterized by marked genomic instability and progressive clonal evolution, particularly in the relapsed/refractory setting. Here, we report a case of aggressive relapsed/refractory MM in which next-generation sequencing (NGS) revealed spatio-temporal clonal heterogeneity after anti-MM treatment. Serial molecular profiling demonstrated dynamic shifts in clonal architecture during successive lines of therapy, highlighting the selective pressure exerted by treatment and the emergence of resistant clones. This case underscores the limitations of traditional cytogenetic approaches, such as conventional karyotyping or fluorescence in situ hybridization, in detecting small subclones and supports the integration of NGS into clinical practice to better characterize molecular heterogeneity and potentially guide therapeutic strategies in high-risk MM.