Current standards for first-line therapy of multiple myeloma

Current standards of care for first-line treatment of multiple myeloma are evolving rapidly because of the introduction of regimens based on novel agents with unique mechanisms of action: the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide. These regimens are becoming increasingly widely used, offering substantially greater benefit to patients in terms of higher response rates and, more importantly, prolonged response durations and survival compared with established standard first-line treatment strategies. A notable aspect of many of these emerging treatment options is the very high rates of complete response (CR) reported, previously only seen with transplantation-based strategies. Achievement of CR is prognostic for improved overall survival; therefore, the higher rates and quality of responses seen with the new regimens might substantially improve patient outcomes versus established standards of care. For example, addition of each of the 3 novel agents to melphalan/prednisone results in higher overall response rates and CR rates, as well as prolonged progression-free and overall survival, compared with melphalan/prednisone alone. Similar substantial improvements in response are seen with addition of the 3 agents to single-agent dexamethasone and the use of bortezomib or thalidomide in VAD (vincristine/doxorubicin/dexamethasone)-like regimens, as induction therapies before stem cell transplantation and in patients not proceeding to transplantation. Ultimately, these novel regimens might obviate the need for stem cell transplantation in a sizeable proportion of patients. The emergence of these new therapeutic options appears likely to significantly alter the first-line treatment paradigm for patients with multiple myeloma.