Emerging biological insights and novel treatment strategies in multiple myeloma.

INTRODUCTION: Survival in multiple myeloma (MM) has improved significantly in the past 10 years due to new treatments, such as thalidomide and lenalidomide (immunomodulatory drugs or IMiDs) bortezomib and advances in supportive care. Nevertheless, almost all MM patients show disease relapse and develop drug resistance. AREAS COVERED: The authors review the therapeutic approach for untreated MM patients. Furthermore, the prognostic stratification of patients and the proposed risk-adapted strategy are discussed. Finally, preclinical and clinical data regarding newer antimyeloma agents, currently undergoing examination such as proteasome inhibitors (PIs, carfilzomib), IMiDs (pomalidomide), epigenetic agents (histone deacetylase inhibitors vorinostat and panobinostat), humanized monoclonal antibodies (elotuzumab and MOR03087) and targeted therapies (inhibitors of NF-κB, MAPK, HSP90 and AKT) are reported. EXPERT OPINION: MM patient outcome has remarkably improved due to the use of three to four drug combination therapies including PIs and IMiDs, which target the tumor in its bone marrow microenvironment, however MM treatment remains challenging. The use of high-throughput techniques has allowed to discover new insights into MM biology. The identification of candidate therapeutic targets and availability of respective investigative agents will allow for a substantial progress in the development and implementation of personalized medicine in MM.