Current risk stratification and staging of multiple myeloma and related clonal plasma cell disorders

Clonal plasma cell disorders encompass a spectrum of conditions such as multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), Waldenström macroglobulinemia (WM), and immunoglobulin light chain (AL) amyloidosis. In MGUS, SMM, and MM, progression risk varies widely and is influenced by a complex interplay of tumor burden, cytogenetic abnormalities, bone marrow microenvironment, and host factors. Waldenström macroglobulinemia, while usually indolent, presents its own distinct spectrum of molecular abnormalities and disparate clinical outcomes. In AL amyloidosis, clinical trajectories are heavily dictated by the nature and extent of organ involvement. In this review, we provide a comprehensive overview of current risk stratification schema used across the spectrum of clonal plasma cell disorders, highlight the strengths and limitations of major risk stratification frameworks, and provide our recommendations for clinical practice.