There has been marked improvement in the clinical outcomes of myeloma in recent years with the introduction of IMiDs and proteasome inhibitors. IMiDs, thalidomide and lenalidomide have been utilized in all stages of MM treatment – induction therapy in transplant- and nontransplant-eligible patients, posttransplant consolidation and as maintenance therapy after ASCT or conventional chemotherapy. A novel IMiD, pomalidomide, is currently going clinical trials and appears very promising with acceptable toxicity profile and efficacy against myeloma, including in patients with resistance to other IMiDs and the proteasome inhibitor bortezomib. Despite these improvements in outcomes, myeloma remains essentially incurable and almost all patients become unresponsive to treatment secondary to clonal evolution and development of resistance through a variety of mechanisms. CRBN was identified as a primary target of thalidomide teratogenicity. It was subsequently shown to be a key mediator of antimyeloma activity of IMiDs and its absence or downregulation is associated with IMiD resistance. Further studies may allow development of clinically applicable biomarkers to predict response to therapy and/or develop strategies to overcome IMiD resistance. Several new antimyeloma treatments are being evaluated including novel proteasome inhibitors, monoclonal antibodies and others. Proteomic profiling and utilization of high-throughput technology may emerge as potential strategies in the future and aid in individualization of the treatment based on biology of the disease. One can be optimistic that these advances will lead to further improvements and outcomes. IMiDs can be expected to continue to remain crucial weapons in the arsenal to treat myeloma.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Expert Rev Hematol. 2013;6(1):69-82. © 2013 Expert Reviews Ltd.