From the bench to the bedside: emerging new treatments in multiple myeloma
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- Hayden, P.J., Mitsiades, C.S., Anderson, K.C. et al. Targ Oncol (2008) 3: 19. doi:10.1007/s11523-007-0072-3
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Several novel drug classes have been developed for multiple myeloma treatment within the last decade. The immunomodulatory drugs, thalidomide and lenalidomide, and the first-in-class proteasome inhibitor, bortezomib, target not only the malignant plasma cells but also key stromal cell support for the neoplastic clone. All three compounds have proven efficacy in advanced disease and increasing evidence for excellent response rates and clinical benefit in newly diagnosed patients. Attention is now focused on producing rational molecularly based drug combinations, incorporating both novel agents and conventional drugs, to further improve outcome. In the setting of autologous stem cell transplantation, the incorporation of these therapies into transplant-based treatment has recently been shown to result in superior overall survival, as have other combinations in relapsed disease, such as bortezomib with liposomally encapsulated doxorubicin. Several new agents are now in clinical trials or are at advanced stages of pre-clinical studies. These include second generation proteasome inhibitors, as well as inhibitors of heat shock proteins, histone deacetylases, receptor tyrosine kinases, and agents targeting the microenvironment of tumors, including defibrotide.