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The treatment of multiple myeloma is evolving rapidly. Despite the number of regimens and combinations available, there is lack of data from phase III trials demonstrating superiority of one regimen over the other in terms of overall survival and/or quality of life. The only clear survival signals have come from studies that compared newer regimens with historic ones such as melphalan-prednisone (MP) or vincristine-doxorubicin hydrochloride-thalidomide (VAD). Thus, the choice of therapy at present is often made based on physician discretion, bias, and limited data from phase II studies. Further, the regimens available have considerably different profiles in terms of safety, convenience, and cost. Given the dramatic variations in expected outcome depending on the various known prognostic factors, a risk-adapted strategy is required to provide the best available therapy to each patient based on host factors as well as prognostic markers of disease aggressiveness. This article reviews the current status of myeloma therapy and risk stratification. Results from major phase III trials are reviewed, and a risk-adapted individualized approach to therapy is presented and discussed.

Upfront Therapy for Myeloma: Tailoring Therapy across the Disease Spectrum.