Perspectives in the treatment of multiple myeloma.

INTRODUCTION: The development of proteasome inhibitor (PI) and immunomodulatory drugs (IMiDs) and advances in supportive care have considerably changed the treatment paradigm of multiple myeloma (MM) and significantly improved survival. Nevertheless, almost all patients show disease relapse and develop drug resistance.

AREAS COVERED: We review the prognostic stratification and therapeutic strategy for newly diagnosed MM patients. Furthermore, mechanisms of drug resistance are discussed. Data regarding newer drugs, currently undergoing examination, such as PI (carfilzomib, ONX0912, MLN9708, and marizomib), IMiDs (pomalidomide), histone deacetylase inhibitors (vorinostat and panobinostat), kinase inhibitors (temsirolimus, everolimus, and tanespimycin), and immune-based therapies (elotuzumab, siltuximab, MOR03087, and MMBT062) are reported.

EXPERT OPINION: The use of three to four drug combination therapies including PI and IMiDs has significantly impacted on MM patient outcome. Moreover, new insights into MM biology from high-throughput technologies and availability of newer and more efficacious drugs will continue to influence our approach to MM treatment. In the immediate future molecular subgroup-specific trials using targeted agents may represent a very important step toward evaluating impact of interfering with relevant signaling pathways in MM. With the continued rapid evolution of progress in this field, MM will become a chronic illness having sustained complete response in a significant number of patients.