Lenalidomide, a second generation immune-modulatory agent, is intended for the treatment of red blood cell transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome (MDS) associated with a deletion 5q (del(5q)) cytogenetic abnormality. In the U.S., the drug was licensed for this indication based on a phase II trial. The European Medicines Agency, on the other hand, has not granted market authorisation for this indication, because of lack of comparative data for the risk of acute myeloid leukaemia (AML) progression.

The efficacy of two different dosing regimens (10mg and 5 mg) of lenalidomide was assessed in a recent phase III trial in comparison to placebo. Red blood cell-transfusion independence, the primary endpoint, cytogenetic responses as well as short-term health-related quality-of-life outcomes were achieved more often in the lenalidomide groups than in the placebo group. Short-term risk that is at 16 weeks for progression to AML was 3% in the placebo and in the lenalidomide 5mg group and 0% in the lenalidomide 10mg group. Data for median OS are reported but are not meaningful due to cross-over. Higher grade adverse events were more common in the lenalidomide groups than in the placebo arm.

It seems as patients can benefit from lenalidomide at the expenses of severe AEs and potential secondary cancers. Thus further refinement of criteria for patient selection, close observation and follow-up investigations to identify non-responders are basic prerequisites to avoid exposure to lenalidomide therapy and potential secondary tumours of patients who do not benefit from this therapy.