Immunomodulatory drugs in the treatment of myelodysplastic syndromes

Abstract

Purpose of review: The aim of this article is to discuss the proposed mechanisms of action, clinical trial data, and clinical implications for use of the immunomodulatory drugs in the treatment of myelodysplastic syndrome.

Recent findings: The immunomodulatory drugs are a novel, nonteratogenic class of thalidomide analogues that are more potent and less toxic than the parent compound. Lenalidomide, a second generation immunomodulatory drug, has shown substantial remitting activity in myelodysplastic syndrome that is karyotype-dependent. Its biologic effects include T-cell co-stimulation, promotion of erythropoiesis, angiogenesis inhibition, and modulation of apoptosis. Results from the MDS-003 multicenter deletion 5q registration study show that lenalidomide suppresses the deletion 5q clone, and in higher risk myelodysplastic syndrome patients, may also alter the natural history of disease. Lenalidomide was approved by the US Food and Drug Administration for the treatment of International Prognostic Scoring System low or intermediate-1 risk myelodysplastic syndrome patients with chromosome 5q deletion. The most common adverse events with lenalidomide therapy are neutropenia and thrombocytopenia, the frequency of which is highest in patients with deletion 5q, in whom early clonal suppression is expected. Combination strategies are now in progress, which may improve the therapeutic potential of the immunomodulatory drugs.

Summary: The immunomodulatory drugs show exciting erythropoietic activity in myelodysplastic syndrome that is karyotype-dependent.