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[摘要]：Pomalidomide (CC-4047) is an immunomodulatory drug (termed IMiD (R)) that is structurally related to thalidomide and exhibits multimodal anticancer activity and is in late-stage clinical development for the oral treatment of refractory multiple myeloma (MM) and myeloproliferative neoplasm-associated myelofibrosis. Early data suggest efficacy for this drug in MM, with up to 49% overall response rates with pomalidomide combined with dexamethasone in patients refractory to both lenalidomide, an IMiD (R) structurally related to pomalidomide and thalidomide, and bortezomib, a reversible proteasome inhibitor. Response rates in myeloma are measured as the sum of the clinical responses divided by the number of patients studied and include maintenance, decrease or complete removal of serum abnormal myeloma antibodies (M-component) and maintenance, partial or complete eradication of malignant plasma cells in the bone marrow. In myelofibrosis, a 36% overall response rate (measured by maintenance, partial or complete reduction in bone marrow fibrosis and cancer cells, reduction of spleen enlargement and improvement or normalization of anemia) was observed for a cohort of patients on low-dose pomalidomide with prednisone. In 2009, pomalidomide received orphan drug status in the E.U. for the treatment of multiple myeloma, and it has also received orphan drug designation for myelofibrosis. The following article describes the history of pomalidomide, its preclinical pharmacology and mechanisms of action, clinical studies undertaken so far and its potential overall as a multimodal anticancer agent. |
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