Management of relapsed and refractory multiple myeloma: literature review and our data. Part III

Advances in treatment options for patients with multiple myeloma have made a significant impact on overall survival and have helped to achieve the rates of response and duration of remission previously not unachievable with standard chemotherapy-based approaches. These improvements are due, in a large part, to the development of the novel agents, including bortezomib, thalidomide, and lenalidomide, each of which has substantial single-agent activity. Combinations of bortezomib, thalidomide, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. However, when patients are unresponsive to immunomodulatory drugs and bortezomib, the prognosis becomes poor. A number of novel agents are being tested in multiple myeloma, but relapsed/refractory multiple myeloma still represents a challenge and difficult area for drug development. Therefore, the new agents are needed. In addition, a large number of second- or third-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. Such agents as carfilzomib, pomalidomide, vorinostat, panobinistat, romidepsin, perifosine, tanespimycin, bendamustine, and elotuzumab are just a few out of many exciting new compounds that are being tested in phases I, II, or III of clinical trials for relapsed patients. This review covers the new strategies, based on clinical trials and our own data and intended for optimizing treatment outcomes in relapsed/refractory multiple myeloma. We describe the various classes of novel drugs under investigation and discuss the pros and cons of the data obtained in preclinical and clinical studies. The adverse effects of the new drugs are presented in detail.