Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression.

Lenalidomide consistently induces transfusion independence and complete cytogenetic response in patients with myelodysplastic syndromes with 5q deletion. Only limited information on long-term outcome is currently available. We performed a long-term follow-up analysis of 42 patients with low or intermediate risk myelodysplastic syndromes and 5q deletion treated with lenalidomide. At a median follow-up of 40 months, 58% of the patients achieved an erythroid response and 48% a cytogenetic response. Thirty-six percent of patients progressed into acute myeloid leukaemia. 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 increased risk of leukaemic transformation. However, erythroid and cytogenetic responders had a significantly decreased risk of progression to acute myeloid leukaemia (p = 0.001 and p = 0.009, respectively) compared to non-responders. Three and 5 years after study entry, the cumulative incidence of acute myeloid leukaemia 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) myelodysplastic syndromes without erythroid or cytogenetic remission after treatment with lenalidomide have a high risk for clonal evolution and acute myeloid leukaemia 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) myelodysplastic syndrome patients treated with lenalidomide may help to identify patients requiring alternative treatment strategies.