Novel agents and new therapeutic approaches for treatment of multiple myeloma

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.

Figure 1

Progress in the treatment of multiple myeloma[127].

Figure 2

Chemical structure of bortezomib and new proteasome inhibitors carfilzomib, delanzomib (CEP18770), marizomib (NPI-0052) and ixazomib (MLN9708).

Figure 3

Chemical structures of thalidomide and its analogues, lenalidomide (CC-5013) and pomalidomide (CC-4047).