Risk stratification in multiple myeloma, part 2: the significance of genetic risk factors in the era of currently available therapies.

Multiple myeloma (MM) is a heterogeneous disease, and a variety of risk factors at the time of initial diagnosis can be used to stratify patients. In the first part of this 2-part series, we reviewed the currently identified prognostic factors, characterized by disease burden, host factors, tumor biology, and depth of response to therapy. However, these risk factors cannot be interpreted independently of therapies. Novel therapies have the potential to worsen or improve outcomes compared with conventional therapy in high-risk patients, or actually overcome the high-risk status, thereby resulting in reclassification as standard risk. For example, thalidomide (Thalomid, Celgene) is associated with worse outcomes in patients with high-risk cytogenetic abnormalities, such as deletion of chromosomes 13 and 17p, whereas proteasome inhibitors appear to overcome t(4;14). The second part of this series reviews the significance of various genetic risks in the era of novel therapies for MM.