Seminars in hematology
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Seminars in hematology · Oct 2005
ReviewManagement of the relapsed/refractory myeloma patient: strategies incorporating lenalidomide.
The immunomodulatory drug (IMiD) lenalidomide is a more potent immunomodulator than thalidomide with respect to its effects on cytokine modulation and increased T-cell proliferation. Of all the IMiDs, clinical trial data are most mature for lenalidomide. In phase I studies, dose-limiting toxicities of lenalidomide were limited to myelosuppression and a response rate of 72% was seen in relapsed/refractory patients. ⋯ Thrombocytopenia was a significant grade 3 or 4 toxicity observed; however, it was manageable with dose reduction. In contrast with high-dose dexamethasone, deep vein thrombosis has emerged as an important toxicity. Lenalidomide is currently being tested in combination with both standard and novel agents, including bortezomib, for patients with relapsed/refractory multiple myeloma.
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Seminars in hematology · Oct 2005
ReviewLenalidomide and thalidomide: mechanisms of action--similarities and differences.
Multiple myeloma is a B-cell malignancy characterized by an excess of monotypic plasma cells in the bone marrow. The molecular mechanisms that are involved in disease progression depend on the interaction between the multiple myeloma cells and the bone microenvironment. Because these mechanisms have been well characterized, it is possible to develop regimens that are more specific to pathways involved in the pathogenesis of multiple myeloma than is typical for conventional chemotherapy in disease management. ⋯ Although thalidomide and IMiDs demonstrate similar biologic activities, IMiDs are more potent than thalidomide and achieve responses at lower doses. Lenalidomide, a thalidomide derivative, has also been shown to have a different toxicity profile. Our understanding of the mechanism of action of these agents has provided a platform for exciting clinical trials evaluating combinations of thalidomide and lenalidomide with both conventional chemotherapy and newer targeted agents.