Management Strategies for Relapsed Multiple Myeloma

Multiple myeloma is the second most common hematologic malignancy after non-Hodgkin lymphoma. Numerous treatments for this disease are available, but despite high overall response rates, relapse occurs in almost all patients, and survival has typically been no more than 5 years. Treatment options for relapsed patients include pulsed dexamethasone; cyclophosphamide-based therapy; doxorubicin-based regimens; melphalan and prednisone; thalidomide with or without dexamethasone; bortezomib; and high-dose chemotherapy supported by autologous or allogeneic stem cell transplantation. Relapsed disease is more difficult to treat, and patients characteristically become resistant to therapy. As a result of the numerous potential complications of multiple myeloma, including fatigue, bone pain, renal dysfunction, increased susceptibility to infection, and spinal cord compression, quality of life has a significant role in the choice of therapy. New strategies in the treatment of relapsed disease are focusing on therapy that is targeted to various cell-signaling pathways and microenvironmental interactions involved in the pathogenesis of multiple myeloma. As they become available, these strategies are showing promise in the treatment of both relapsed and refractory disease, the most recent being the potent thalidomide analog lenalidomide. Research efforts are also concentrated on improving front-line therapy to reduce the rate of relapse so that, ultimately, survival may be extended and patient outcome improved.