Patients with Del(5q) MDS Who Fail to Achieve Erythroid or Cytogenetic Remission After Treatment with Lenalidomide Have An Increased Risk for Clonal Evolution and AML Progression.

Abstract 3818

Poster Board III-754

Lenalidomide consistently induces transfusion independence and complete cytogenetic response in patients with low and intermediate risk myelodysplastic syndromes (MDS) with 5q deletion. Only limited information on long-term outcome of patients treated with this novel approach is currently available. We performed a long-term follow-up analysis of 42 patients with low or intermediate risk MDS and 5q deletion treated with lenalidomide. At a median follow-up of 40 months, 58% of the patients achieved an erythoid response and 48% a cytogenetic response. 36% of patients progressed into acute myeloid leukaemia (AML). Most of them (87%) acquired chromosome aberrations in addition to the 5q deletion, i.e. underwent clonal evolution during leukaemogenesis. There were no clinical, cytological or cytogenetic markers at study entry that allowed prediction of an increased risk of leukaemic transformation. However,erythroid and cytogenetic responders had a significantly decreased risk of progression to AML (p=0.001 and p=0.009, respectively) compared to non-responders. 3 and 5 years after study entry, the cumulative incidence of AML for patients with a cytogenetic response was 10% and 21%, respectively, and for patients without cytogenetic response, it was 46% and 60%. Patients with del(5q) MDS who fail to achieve erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression. In refractory, or relapsing, patients, genetic instability and clonal evolution seem to be the driving forces of leukaemic transformation. Regular follow-up investigations of del(5q) MDS patients treated with lenalidomide may help identifying patients needing alternative treatment strategies.