Rituximab and Lenalidomide vs Rituximab Alone as Maintenance After R-chemoterapy for Relapsed/Refractory FL Patients

Inclusion Criteria: * Follicular lymphoma grade I, II and IIIa according to the WHO classification. Rebiopsy at study entry is strongly encouraged but mandatory only in case of suspected transformation (elevated LDH or rapidly-growing disease or unusual relapse presentation). * First or second relapse or progression following R-chemotherapy (Rituximab maintenance and IF radiotherapy are not considered treatment lines). * Previous treatment with Bendamustine can be considered eligible if relapse occurred after ≥ 24 months. * Age \>18 years. * Patients not eligible for high dose chemotherapy and ASCT because of: age ≥ 65 years, impaired PS or organ function due to major comorbidities or relapsed or refractory disease after previous ASCT before 65 of age. * Stage II, III or IV according to Ann Arbor at relapse. * Need of treatment according to SIE-SIES-GITMO guidelines for follicular lymphoma: stage II-IV with systemic symptoms, high tumor burden (i.e. \>3 lymph nodes measuring \>3 cm or a single lymph node \>7 cm), extranodal disease, cytopenia due to marrow involvement, spleen involvement (≥16 cm by CT), leukemic phase, serious effusion, symptomatic or life endangering organ involvement, rapid lymphoma progression, consistently increased LDH levels. * Must be able to adhere to the study visit schedule and other protocol standards. * ECOG performance status ≤ 2 (except when PS impairment is related to lymphoma). * Be willing and able to comply with the protocol for the duration of the study. * Absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L unless due to marrow involvement by lymphoma; and platelets count ≥ 75 x 109/L unless due to marrow involvement by lymphoma. * Calculated creatinine clearances ≥ 40 ml/min. * Agree to be using effective contraception for the entire treatment period according to standard guidelines for patients receiving lenalidomide Exclusion Criteria: * Any lymphoma subtype other than FL including transformed FL * Grade 3b follicular lymphoma. * Radiotherapy within 3 months prior to study entry * Major surgery (excluding lymph node biopsy) within 28 days prior to registration. * HIV positive serology. HBV and HCV positive patients will be not excluded from the study if the hepatic enzymes are within the ranges later defined. HBV occult carriers patients will be given lamivudine as prophylaxis starting one week before chemotherapy. HbsAg, HBcAb, HBV-DNA and HCV-RNA levels will be monitored twice every month in HCV or HBV positive patients. * Life expectancy \< 6 months. * Known sensitivity or allergy to murine products. * Prior history of malignancies, other than follicular lymphoma, unless the subject has been free of the disease for \> 3 years with the exception of adequately cured localized non-melanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast or incidental histological finding of prostate cancer (TNM stage of T1a or T1b) * Prior use of lenalidomide. * Neuropathy \> Grade 1. * Myocardial infarction within the last 6 months * Presence or history of CNS involvement by lymphoma. * Subjects who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis. * Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) \> 3x upper limit of normal (ULN), except in subjects with documented liver involvement by lymphoma * Total bilirubin \> 2.0 mg/dl (34 umol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or lactating females. * 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 which confounds the ability to interpret data from the study.