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Rochester, MN, USA
by Lynne Lederman, PhD
The ability to predict patient response to therapy would allow individualization of therapy; only patients expected to respond well to a particular treatment would then be exposed to the potential toxicity of the treatment. The ability to target therapy to myeloma genetic type does not yet exist. GEP yields a molecular portrait of a large number of genes that may be useful in diagnosis, stratification, prediction of response based on the profile, and an indirect assessment of IgH locus translocations. GEP may provide three types of information related to drug response: the individual genes expressed in responders vs. non-responders, IgH translocations, and the presence of functional pathways. A GEP profile has been done on CD138+ cells isolated from 30 patients receiving thalidomide and dexamethasone as initial therapy on the ECOG phase 2 or 3 trials, and identified 25 genes that separated responders from non-responders; 15 of these genes were unique and included structural, immune regulation, adhesion, and apoptosis regulatory genes. There was a correlation with lack of IgH translocation and response to therapy. GEP analyses of other patients populations in different studies using different chips and different drugs have identified other sets of genes associated with response to treatment, supporting the use of this approach. Dr. Kumar plans to carry out an analysis to identify genes associated with response to lenalidomide.