The term high-risk multiple myeloma is aimed to identify a heterogeneous group of patients who are more likely to progress and die early of their disease. Therefore, recognition of these patients is crucial. With the increase in the number of treatment options, the outcome for high-risk patients has probably improved, although the true extent of this improvement remains unknown, due to both the heterogeneous components of high-risk disease and its under-representation in clinical trials. In this article, we review the definitions of high-risk disease, emphasizing the fact that no single definition can represent the entire high-risk population. In the second part, we review the treatment options available for the management of high-risk myeloma as well as our general approach for high-risk disease. In light of the poor prognosis associated with high-risk myeloma, even in the current era, new approaches for the management of this subset of patients are needed.
Keywords: Resistance; combination therapy; early-death; prognostication; progression; transplant.