Lenalidomide for Myelodysplastic Syndrome Refractory to Hypomethylating Agents

Inclusion Criteria: * Patient must be able to understand and voluntarily sign an informed consent form. * Patient must be ≥ 18 years old. * Patient must be able to adhere to the study visit schedule and other protocol requirements. * Patient must have histologically confirmed Myelodysplastic Syndrome as defined by FAB Classification including CMML and secondary MDS which has either: * progressed at any time during treatment with hypomethylating agents * failed to achieve a response after 6 cycles * progressed after treatment with hypomethylating agents had been discontinued Criteria for response and for progression as defined by revised IWG criteria * Patient must have discontinued all previous cancer therapy, including radiation, hormonal therapy and surgery at least 4 weeks prior to treatment in this study. * Patient must have an ECOG performance status of ≤ 2 at study entry * Patient must have laboratory test results within these ranges: * calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula * total bilirubin ≤ 1.5 x ULN * AST (SGOT) and ALT (SGPT) ≤ 3 x ULN * Patient must be disease free of prior malignancies for at least 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. * Patient must be registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®. * If a female of childbearing potential (FCBP), patient must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to initiation of therapy and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days). Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. A FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). -If a FCBP, patient must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal \[birth control pills, injections, or implants\], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed Exclusion Criteria: * Patient must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Patient must not be pregnant or breastfeeding. * Patient must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Patient must not use any other experimental drug or therapy within 28 days of baseline. * Patient must not have a known hypersensitivity to thalidomide. * Patient must not have developed of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Patient must not have any prior use of lenalidomide. * Patient must not be concurrently using other anti-cancer agents or treatments. * Patient must not have known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.