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Multiple myeloma is characterized by clinical and biologic heterogenicity. Recently, genetic analysis has provided predictable prognosis across different types of treatment. These advances have allowed patients to be categorized into different risk groups and have been particularly useful in defining a high-risk group with short survival after standard- and high-dose chemotherapies. Preliminary studies have shown promising outcomes after the use of novel agents, such as bortezomib, thalidomide, and lenalidomide in high-risk patients, including those eligible for autologous stem cell transplantation and those who cannot or will not undergo transplantation. The application of risk-based therapy and the potential of the new agents to abrogate the influence of adverse prognostic features may improve outcomes in these patients.

Maintenance therapy in multiple myeloma has been under investigation for more than 3 decades, without evidence of clear benefit until recently. Chemotherapy maintenance offers no benefit after conventional or high-dose treatment. Interferon-based maintenance is associated with minimal improvements in clinical outcomes, but is poorly tolerated. Results of corticosteroid maintenance studies have been conflicting; at least one randomized trial showed improved survival with prednisone maintenance after conventional chemotherapy. The role of the novel agents thalidomide, lenalidomide, and bortezomib as maintenance is emerging. Most reported maintenance studies have evaluated thalidomide, alone or in combination with a corticosteroid. Several of these studies suggest that thalidomide-based maintenance prolongs overall survival after autologous stem cell transplantation. Important questions that have not yet been resolved include the optimal dose and duration of thalidomide, whether clinical benefit depends on response to induction therapy and risk for relapse, and whether reported benefits are caused by cytoreduction or eradication of minimal residual disease, especially with bortezomib maintenance. Ongoing randomized trials are evaluating lenalidomide and bortezomib maintenance therapies to better define the role of these drugs as maintenance in multiple myeloma.

Venous thromboembolism (VTE), osteonecrosis of the jaw, renal failure, and anemia are all common complications of multiple myeloma therapy. Many of these adverse events have been documented only in the past 5 to 10 years, in conjunction with the introduction of a series of the newer therapies thalidomide, bortezomib, and lenalidomide. This article discusses these complications in detail and provides strategies for health care providers to best prevent, identify, and manage them. Preventive measures, such as VTE prophylaxis and appropriate dental hygiene, as well as patient education, dose adjustments, limited duration of drug treatment, and consideration of therapies that are associated with less burdensome adverse-event profiles, can contribute to substantially improved outcomes and quality of life.