A rational approach to functional high-risk myeloma.

Multiple myeloma is a clinically and biologically highly heterogeneous disease, as the overall survival can vary from more than a decade in patients with standard risk disease treated with intensive chemotherapy to 2-3 years in patients with high-risk features. The current staging systems, which rely on baseline biological risk factors to stratify patients into groups with differing risks of progression or death, are sometimes suboptimal tools for identifying high-risk patients. This is particularly evident when considering the so-called functional high-risk patients-patients who do not necessarily display baseline high-risk features but typically show a suboptimal response to induction therapy or relapse early after treatment initiation: the survival of these patients is particularly poor even in the context of newer therapies. The prompt identification, as well as a consistent definition, of this subset of patients, as well as their management, currently represents an unmet medical need. In this review we explore the main characteristics of functional high-risk patients, the available known risk factors and scoring systems, and the possible management.