G. David Roodman

Veterans Affairs Pittsburgh Healthcare System, Department of Medicine/Hematology-Oncology, Pittsburgh, Pennsylvania; and University of Pittsburgh, Department of Medicine/Hematology-Oncology, Pittsburgh, Pennsylvania, U.S.A.

Abstract

Myeloma is the most frequent malignancy to involve the bone. The bone microenvironment plays an important role in supporting tumor growth, bone destruction and resistance to chemotherapy. Until the advent of novel therapies such as bortezomib, the prognosis for patients with myeloma did not change significantly over 40 years. The median survival of patients until 1996 was approximately 30 months, and has now improved to almost 5 years. Bortezomib is the first-in-class proteasome antagonist approved for treatment of myeloma. It is active in newly diagnosed, relapsed and refractory patients and is now being used as a platform for combinations with other new agents for myeloma. Its major side effects include neuropathy and thrombocytopenia. In addition to its anti-myeloma effect, bortezomib also targets the bone microenvironment and can inhibit osteoclast formation, and stimulate osteoblast activity in patients with myeloma. Potentially, combination of bortezomib with other agents that stimulate bone formation or block bone resorption will further enhance the anti-myeloma effects of bortezomib and overcome the contribution of the tumor microenvironment to myeloma growth.