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01-09-2015 | Staging | Article

Defining and treating high-risk multiple myeloma

S Z Usmani, P Rodriguez-Otero, M Bhutani, M-V Mateos, J S Miguel


Multiple myeloma (MM) is more recently being recognized as a heterogeneous group of disease with variability in outcomes based on specific clinical and biologic predictors. MM patients can be broadly categorized into standard, intermediate and high risk for disease relapse, morbidity and mortality. The high-risk features include patient-specific factors such as old age, poor performance status and comorbidities; clinical features such as primary plasma cell leukemia and extramedullary disease; disease-specific biologic features such as deletion 17p, t(4;14) and high-risk gene expression profiling signatures. The current paper reviews the available data on best therapeutic approaches for high-risk MM.

Leukemia 2015; 29: 2119–2125. doi: 10.1038/leu.2015.209

The survival of multiple myeloma (MM) patients has significantly improved over the past two decades, first through the introduction of autologous stem cell transplant (ASCT), and more recently due to the use of proteasome inhibitors (bortezomib and carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). However, this improvement has not been uniform, with some patients achieving long-term remissions being probably already cured, whereas others having dismal prognosis with a very short survival. This heterogeneity is related to either host features or specific characteristics of the tumor. A stable treatment paradigm for the management of MM has allowed for analysis of discrete variables that predict response and survival. Over the past 20 years, cytogenetics and International Staging System (ISS) are the two well-studied variables that have been primarily used to assign high-risk disease, a subset that constitutes a sizeable percentage of all patients and presents an unmet therapeutic challenge. By defining high-risk biologic and clinical variables, a strong case can be made for a more precise counseling of the patients regarding their disease prognosis, and for treating patients with investigational agents within the framework of risk-adapted clinical trials. In this paper, we review updated understanding of the most relevant factors that define high-risk subtype of MM represented by a survival of less than 3 years. In addition, we discuss treatment strategies that can be offered to these patients and how initial evaluation can be used to inform the choice of treatment.

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