Bortezomib in the upfront treatment of multiple myeloma

Abstract

Although multiple myeloma (MM) remains a disease that is incurable with conventional treatments, important changes have recently been introduced in the management of the disease as a result of advances in our knowledge of its pathogenesis and the availability of novel agents. Bortezomib is a first-in-class proteasome inhibitor that targets not only the MM cell but also its interaction with the bone marrow microenvironment. It represents an excellent example of a novel class of agents that have quickly moved from the bench to the bedside. Four randomised trials have evaluated the role of bortezomib-based combinations as an induction therapy in transplant candidate myeloma patients, revealing a high efficacy (>80% response rate, with 20-30% complete response (CR)) that increased after autologous stem cell transplant, confirming the results of numerous pilot studies of various bortezomib-based combinations. In patients who are not candidates for transplant, bortezomib in combination with melphalan and prednisone has also proved to be superior to conventional therapy, with high overall and CR rates and a significantly longer time to progression and overall survival. Moreover, new strategies are being explored in patients who are not candidates for transplant based on the optimisation of the VISTA schedule and using weekly doses of bortezomib to improve tolerability. Overall, these results have established bortezomib-based combinations as key treatment options for newly diagnosed myeloma patients. © Springer Basel AG 2011.