, Volume 3, Issue 1, pp 47-66
Date: 10 Aug 2012

Treatment of Multiple Myeloma

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Abstract

The management of multiple myeloma (MM) has undergone many developments in the last 30 years. Initially, melphalan was used as a single agent and this was followed by the discovery of corticosteroids as highly active agents and the design of multiagent cytotoxic regimens. However, although response rates have improved, little impact has been achieved on survival. Interferon has been extensively examined in early as well as relapsed disease. Currently, a benefit in survival is only evident in maintenance phase, where there is a small but significant difference. However, this has to be evaluated in the context of adverse effects and the impact on quality of life.

In recent years, autologous stem cell transplantation has become established as the standard therapy for eligible patients. An advantage in survival has been established in at least one randomized trial, and response rates have been improved. Unfortunately, relapse after an auto transplant is almost inevitable, and the possible benefits of more than one transplant continue to be examined. To date, allotransplantation has assumed a much smaller role in MM, predominantly because of a high transplant-related mortality (TRM). An important innovation has been the use of donor lymphocyte infusions to harness the graft versus myeloma effect, either in relapse after allogeneic transplantation or in the novel strategy of nonmyeloablative allotransplants, with the aim of reducing TRM and increasing the eligibility of patients for allogeneic transplantation. Thalidomide, which has immunomodulatory and antiangiogenic properties, has been used as a single agent or in combination with other cytotoxic regimens in relapsed/ refractory disease, with response rates of approximately 30%. Its role in early disease is currently being evaluated. Bisphosphonates are now established as standard therapy in myeloma bone disease and are associated with the reduction of skeletal complications. Possible benefits in early ‘smoldering’ disease and effects on survival continue to be evaluated. Immunotherapy is one of the most intensely studied and promising developments in myeloma management. A variety of techniques ranging from tumor vaccination to the use of monoclonal antibodies are under active evaluation. Other experimental agents include the development of proteosome inhibitors, immunomodulatory thalidomide analogs, other antiangiogenic agents, arsenic trioxide, antisense oligonucleotides, anti-bone resorption agents such as osteoprotegerin and farnesyl transferase inhibitors, which are currently at preclinical or early clinical phases of investigation.