Novel agents for previously untreated multiple myeloma

For decades, chemotherapy for multiple myeloma has consisted of standard combinations of alkylating agents, anthracyclines, and steroids with or without hematopoietic stem cell rescue. While these therapies can provide rapid responses and result in modest gains for patients, the disease eventually relapses in all patients and becomes resistant to treatment. More recently, agents with novel mechanisms of action, such as the proteasome inhibitor, bortezomib and immunomodulatory drugs like thalidomide and its derivative lenalidomide, have shown promise for treatment of patients with not only refractory and relapsed disease, but also for those with previously untreated multiple myeloma. Recent combinations of these agents (thalidomide, bortezomib, lenalidomide) with or without alkylating agents, anthracyclines, and steroids have produced rapid remissions (within 1-3 cycles) resulting in improved overall response rates of 75-95% and complete response rates of 5-25% in patients receiving induction therapy (1-11). Initial data with the combination of melphalan-prednisone-thalidomide demonstrates improved overall survival in elderly patients compared with melphalan-prednisone and reduced intensity myeloablative therapy with autologous stem cell support, and provides the first suggestion that the improvement in overall response rates with novel agent combinations for induction therapy is likely to translate into an overall survival benefit for many patients with multiple myeloma (12). Thus, these regimensmay provide a useful alternative or adjunct to myeloablative therapy with stem cell transplant in the future. This chapter will focus on the role of bortezomib, thalidomide and lenalidomide in induction therapy of multiple myeloma.