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Treatment of Plasma Cell Dyscrasias With Thalidomide and Its Derivatives

From the Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece; and Department of Lymphoma/Myeloma, The University of Texas M.D. Anderson Cancer Center, Houston, TX.

Address reprint requests to Meletios A. Dimopoulos, MD, 227 Kifissias Ave, Kifissia, Athens 14561, Greece; e-mail: mdimop{at}med.uoa.gr.

Purpose: In 1999, investigators reported promising results of a phase II study of thalidomide in patients with resistant multiple myeloma (MM). Since then, various trials of thalidomide alone and in combination with other agents have been tested in patients with resistant and, more recently, untreated MM. In addition, preliminary results of phase I studies of the immunomodulatory derivatives (IMiDs) of thalidomide have been recently reported.

Design: We reviewed and report the results of clinical trials of thalidomide and the IMiDs, as well as the pharmacology, mechanism of action, and toxicity of these agents.

Results: Thalidomide has demonstrated significant activity in both resistant and previously untreated multiple myeloma. Combination therapy with dexamethasone increases response rate, even in patients previously resistant to both drugs given as single agents. More recent studies of thalidomide with dexamethasone in previously untreated patients are highly encouraging. The addition of chemotherapy to thalidomide and dexamethasone may further increase response rates, but its effect on patient survival has not been clarified. Preliminary results of trials of IMiD-3 indicate that this agent is active in resistant myeloma and has a toxicity profile different from that of thalidomide.

Conclusion: Many studies have confirmed the activity of thalidomide in MM, as well as an improved response with dexamethasone. Newer thalidomide derivatives with reduced toxicity (neuropathy, teratogenicity) are also promising. Thalidomide with dexamethasone may now represent the treatment of choice for previously untreated patients. Further studies with these and other novel agents early in the course of myeloma may improve complete remission rates and frequency of long-term control.

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