Pathogenesis and treatment of extramedullary disease in multiple myeloma: current status, challenges and opportunities

Extramedullary disease (EMD) represents an aggressive manifestation of multiple myeloma (MM) in which malignant plasma cells acquire the ability to survive independently of the bone marrow microenvironment. Based on the site of involvement, EMD is classified into extramedullary bone related (EMB) that partially depends on the bone marrow, and extramedullary extraosseous (EME) that spreads through bloodstream. EMD can affect any tissue or organ and is associated with poor clinical outcomes in patients with MM. The underlying pathogenesis of EMD remains incompletely understood, and no standardized treatment approach has been established to date. This review integrates recent advances in the molecular pathogenesis of EMD with emerging immunotherapeutic strategies, particularly CAR-T cell-based therapies, and discusses the major translational challenges and future directions for improving the management of EMD.