Abstract Abstract 115 Background: Treatment with lenalidomide in patients with low risk MDS with deletion del(5q) has resulted in a high proportion of transfusion independence and also cytogenetic responses. The aim of this study was to evaluate the effect of lenalidomide in high risk MDS and AML patients with del(5q) or monosomy 5 not eligible for induction treatment, primary cases as well as patients relapsing/refractory to intensive treatment. Methods: This investigator-initiated prospective phase II study assessed the effects of continuous lenalidomide treatment during 16 weeks, in increasing doses from 10 to 30 mg, with 8 weeks on the highest level. Dose modifications due to hematologic toxicity were performed according to the clinical judgment of the treating physician. The primary objective was cytogenetic response, assessed by FISH on bone marrow (BM) smears at inclusion and after 8 and 16 weeks. Clinical and morphological BM response was evaluated every 4 weeks. Results: 25 patients were included from October 2007 to July 2009, 22 of which are so far evaluable. Overall, the patient cohort included several patients with very advanced disease and two patients died before treatment was started. Fourteen MDS patients and 11 AML patients have been included. Twenty-two of the patients had 5q- (9 of these had a complex karyotype and 5 had del(5q)+1) and 3 patients had monosomy 5 (all complex karyotype). The median time of treatment was 13 weeks (range 0–16 weeks). The reason for early termination in the patients who started lenalidomide treatment was progressive disease (3) and adverse events (10). Six of 7 patients who completed the study (16 weeks of treatment) had a response: Two MDS patients with del(5q-)+1, and del(5q)+2, respectively, achieved a major cytogenetic response (≥50 % reduction), in one of these patients the blast count decreased from 9.5% to <5%. Two MDS patients with 5q- and complex karyotype had a minor cytogenetic response (≥25% reduction) and a reduction to <5% blasts, respectively. One AML with 5q- and a complex karyotype had a minor cytogenetic response and a complete BM response. Another AML patient with isolated 5q- showed a complete BM, but no cytogenetic response. In total, 6 of the 20 patients (30%) who started treatment had a cytogenetic and/or morphological BM response. Four of 6 responders also experienced hematologic response. Twenty-one serious adverse events (SAE) have been reported in 15 of the patients. The main SAE criterion has been inpatient hospitalization. Fourteen of the SAE:s were infection or febrile neutropenia. In 6 patients the outcome of the SAE has been death. For these patients the causality/relationship to lenalidomide has been judged as not suspected or not related. The cause of death has been the underlying disease or complications to the underlying disease like infections. Conclusion: Lenalidomide as a single agent, but in higher doses than those applied to low-risk MDS patients resulted in cytogenetic and/or morphological bone marrow response in 30% of patients with high-risk MDS or AML with del(5q) or monosomy 5. We considered this a promising response rate, considering the high frequency of very advanced patients, and complex karyotypes. The main serious adverse event was infections. Future combinations with cytostatic or hypometylating agents may further improve these results. Disclosures: Möllgård: Celgene: Research Funding. Hellström-Lindberg:Celgene: Research Funding.