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B. Barlogie, F. van Rhee, E. Anaissie, J. Epstein, J. Crowley and J. Shaughnessy
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Background: During the past 15 years, there has been tremendous progress in the primary and salvage management of patients afflicted with multiple myeloma (MM). Several randomized and historically controlled trials have demonstrated that melphalan (MEL)-based high-dose therapy with autologous hematopoietic cell support effects, in comparison to standard-dose regimens, superior rates of complete response (CR) and, consequently, extended event-free survival (EFS), which translated into overall survival (OS) prolongation in some but not all studies. Tandem autotransplants have further improved clinical outcome in the IFM94 trial. Over the past 5-7 years, several new agents, especially immuno-modulatory drugs [thalidomide and lenalidomide] and the proteasome inhibitor bortezomib, have demonstrated marked salvage potential. When applied up-front, in combination with DEX, each other and especially MEL, unexpectedly high CR rates approaching those after MEL transplants have been reported. Follow-up is too short to be certain about EFS and OS duration. Thus, there is enormous controversy regarding the role, if any, of MEL transplants. Herein we report our collective front-line experience with Total Therapy (TT) regimens, employing as their backbone MEL200-based tandem transplants. As a result of incorporating, in a step-wise fashion, novel agents and treatment principles, all 3 clinical outcome measures (CR, EFS and OS) have been steadily improved. Outcome results will be examined in the context of state-of-the-art molecular genetic features, especially gene expression profiling (GEP) of highly purified plasma cells.