Lenalidomide--a transforming therapeutic agent in myelodysplastic syndromes.

Lenalidomide is an immunomodulatory drug (IMiD) with erythropoietic activity in myelodysplastic syndromes (MDS) that is karyotype dependent. The MDS-003 multicenter registration trial in deletion of chromosome 5q (del[5q]) showed that lenalidomide suppresses the del(5q) clone in patients who achieve transfusion independence and is a prerequisite for sustained restoration of effective erythropoiesis. Long-term outcome data indicate that cytogenetic response to lenalidomide might confer a survival advantage compared with cytogenetic nonresponders, with a corresponding reduced risk for acute myeloid leukemia (AML) progression. In lower-risk, transfusion-dependent patients with MDS without del(5q), lenalidomide has significant, albeit less erythropoietic, activity that could relate to dual effects on both the MDS clone and the bone marrow environment. The most common adverse effects are neutropenia and thrombocytopenia, which occur early and with greater frequency in patients with del(5q), consistent with the drug's action to suppress the MDS clone. Combination strategies are now in both MDS and AML that could further broaden the therapeutic potential of lenalidomide.