Treatment of Relapsed/Refractory Multiple Myeloma

The introduction of several novel and active treatments and improvements in supportive care of myeloma patients has resulted in a prolongation of the survival of these patients. However, myeloma remains an incurable disease and almost all patients will relapse. Effective management of the relapsing/refractory disease incorporates several different strategies, depending on prior treatments, responses, and duration of responses, as well as residual toxicity, age, and physical condition. High-dose dexamethasone still has a role in the management of disease complications such as cytopenias, renal impairment, or spinal cord compression until another agent is added. High-dose therapy may be considered for selected patients who have a long-term treatment-free interval after their first transplantation. Allogeneic transplantation is limited to selected young patients, preferably with an HLA-matched donor. However, the backbone of current strategies for the management of relapsed/refractory myeloma includes the novel agents thalidomide, bortezomib, and lenalidomide. These agents, either with dexamethasone or in combination with chemotherapy, have shown significant activity both in relapsed and in refractory patients. Based on the results of phase III trials, lenalidomide and bortezomib have increased the post-relapse survival and are active in patients who have received prior novel agents; lenalidomide is active in thalidomide-pretreated or bortezomib-pretreated patients and bortezomib alone or in combination with chemotherapy is active in thalidomide/lenalidomide-pretreated patients. Combinations of novel agents show synergistic activity and may overcome drug resistance. Finally, special consideration is needed for the management of patients with renal impairment or other poor prognostic features.