This is a Phase II study to evaluate the efficacy of second-line lenalidomide monotherapy for myelodysplastic syndrome (MDS) patients who failed to hypomethylating agents.

There is no standard therapy after the failure of hypomethylating agents only providing supportive cares including transfusion or cytokine therapies. Lenalidomide is the treatment of choice in case of MDS with 5q deletion. A study of lenalidomide for non-5q deletion MDS patients showed that transfusion independency rate was 26% which was relatively acceptable and suggested that lenalidomide could be used for non-5q deletion MDS patients. There is no datum for second-line lenalidomide therapy after hypomethylating agents. MDS which has highly complex pathogenesis backgrounds will have distinctive subtype for each therapy and each treatment drug can have distinctive subgroup for the response. In fact the investigators don't know which patient will be responsive hypomethylating agents or lenalidomide except for 5q deletion. This suggests that second line therapy after the first line failure in MDS will be different with other type of relapsed/refractory disease which will be tend to more resistant to subsequent therapies. In this regard, there is a possibility to have a relatively high response rate to second line lenalidomide in this selected subset who has failed to the hypomethylation therapy or some patients will be responsive regardless of treatment line. Recent data suggested that MDS with JAK2 mutation will be responsive to lenalidomide. The investigators will analyze the JAK2 mutation status in response evaluation.

Inclusion Criteria:

• Myelodysplastic syndrome by world health organization (WHO) classification
• Treatment failure after hypomethylating agents (HMA; azacitidine or decitabine); Intolerant to hypomethylating agents or Progressive disease after HMA
• Age over 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Adequate organ function (serum creatinine ≤ 2.5 mg/dL, serum aspartate transaminase or alanine transaminase ≤ 3.0 x upper limit of normal (ULN), and serum direct bilirubin ≤ 2.0 mg/dL).

Exclusion Criteria:

• Previous therapy history for MDS except for hypomethylating agents, cytokines (granulocyte-stimulating agents or erythropoietin) or supportive care.
• Patients who cannot keep the strict contraception or who willing to be pregnant.
• Contraindication to lenalidomide: Females who are or may become pregnant; Lenalidomide is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components; Lenalidomide capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
• Patients who cannot take lenalidomide orally
• Current enrollment to other clinical trial
• Presence of uncontrolled bleeding
• Severe or life-threatening other medical conditions
• Any coexisting major illness or organ failure
• Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
• History of congenital or acquired coagulopathy unrelated to malignancy
• History of non-compliance or patient who cannot sign informed consent
• Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
• Candidate of hematopoietic stem cell transplantation who cannot complete 4 cycles of lenalidomide.