High risk versus standard risk

Patients with newly diagnosed or relapsing myeloma can be identified as having standard-risk or high-risk disease. This determination is made based on cytogenetics, genetic aberrations detected by fluorescence in situ hybridization, and possibly the genetic expression profile analyses that are in the process of standardization.[28] Plasma cell leukemia at presentation, or as a leukemic evolution of refractory myeloma, is a particularly high-risk, poor-prognosis entity.[29-33] Plasma cell leukemia with an ultra-high poor prognosis is defined by the presence of more than 2% circulating tumor plasma cells by flow cytometry.[34] Higher-risk patients are candidates for clinical trials using newer agents upfront or newer combination therapies currently used for relapsed disease at the discretion of the clinician.[35-37] Beyond induction therapy, high-risk disease can warrant more aggressive strategies, such as tandem transplant or consideration of allogeneic SCT. More intensive maintenance therapies may also be given for high-risk disease; instead of using lenalidomide alone, lenalidomide plus bortezomib has been chosen based on prior trials using thalidomide.[38] These more aggressive strategies have been implemented because of poor responsiveness to standard regimens and the worse prognosis of high-risk patients. Ultimately, prospective randomized trials are needed to establish improved outcomes with these newer approaches for high-risk patients.