Review
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World J Methodol. Jun 26, 2014; 4(2): 73-90
Published online Jun 26, 2014. doi: 10.5662/wjm.v4.i2.73
Novel agents and new therapeutic approaches for treatment of multiple myeloma
Roberto Ria, Antonia Reale, Angelo Vacca
Roberto Ria, Antonia Reale, Angelo Vacca, Section of Internal Medicine, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, I-70124 Bari, Italy
Author contributions: Ria R, Reale A and Vacca A made a substantial contribution to the conception and design of the manuscript, drafting the article or revising it.
Supported by Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research-AIRC), Investigator Grant and the 5 per thousand Molecular Clinical Oncology Special Program, No. 9965; Milan, to AV, the European Commission's Seventh Framework programme (EU-FPT7) under grant agreement (OVER-MyR) to AV, No. 278706; EU FPT7 (2007-2013) under grant agreement to DR, No. 278570; grants from MIUR PRIN to RR, No. 2009WCNS5C_004; and grants from MIUR PRIN to AV, No. 2010NECHBX
Correspondence to: Roberto Ria, MD, Section of Internal Medicine, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Policlinico, Piazza Giulio Cesare 11, I-70124 Bari, Italy. roberto.ria@uniba.it
Telephone: +39-80-5593106   Fax: +39-80-5478859
Received: November 24, 2013
Revised: January 28, 2014
Accepted: April 17, 2014
Published online: June 26, 2014
Abstract

This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein (immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents (bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality responses with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.

Keywords: Immunomodulators, Multiple myeloma, New drugs, Proteasome inhibitors, Target therapy

Core tip: The aim of this review is to summarize and point out the current therapeutic strategies and the drugs actually in development for the management of multiple myeloma. The rationale of the new treatment strategies is found in their efficacy in targeting tumor cells and their microenvironment. Our understanding of multiple myeloma (MM) pathogenesis including the intracellular mechanisms as well as the interactions between MM cells and their microenvironment has helped the discovery of several targets that have become the focus of drug development. The goal is to improve patient’s survival and to control the disease in a long-term fashion, maintaining the quality of life of our patients.