Multiple myeloma (MM) is a bone marrow- based malignancy of plasma cells that is diagnosed in over 30,000 patients annually in the United States. Despite the many recent advances in the treatment of MM, it remains an incurable disease. Thus, the need for the development of new effective therapies remains critical for these patients.
In general, it has not been shown that patients with smoldering MM (SMM) benefit from early treatment, but recent studies have identified a subset of patients who are at high-risk and may require therapy more quickly. Recent guidelines from the International Myeloma Working Group recommend immediate treatment of this subgroup of SMM. 1 However, although findings in a Spanish study suggested that early treatment of high-risk SMM patients with the immunomodulatory agent (IMiD) lenalidomide and dexamethasone improves overall survival (OS), 2 the design of that study limits its clinical applicability, and no other randomized trials have been completed to show the advantage of early therapy for these patients.
The development of novel agents such as proteasome inhibitors (PIs), IMiDs, histone deacetylase inhibitors (HDACIs), and monoclonal antibodies (mAbs) in recent years has vastly changed the approach to the treatment of MM patients.
PIs that are cytotoxic to MM cells, such as bortezomib, have become a foundation for MM treatment over the past decade. However, patients develop drug resistance to bortezomib by acquiring gene mutations and through other mechanisms. In recent years, newer forms of PIs such as carfilzomib and the oral formulations ixazomib and oprozomib have been and are currently being developed. 3 Preclinical studies have shown that resistance to one PI can be overcome with treatment with another PI. 4
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