This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a brief chemoimmunotherapy with the combination of Rituximab + Bendamustine + Mitoxantrone in elderly patients with advanced stage Follicular Lymphoma.

Inclusion Criteria:

• Histological proven diagnosis of B-cell CD20+ follicular NHL, grade I, II and IIIa of WHO Classification

• Untreated patients with the exception of prior limited radiotherapy

• Stage III or IV who require therapy according to SIE and GELF criteria

• Stage II with at least one of the following:

  • Bulky disease (>7 cm)
  • LDH >normal
  • Systemic symptoms
  • Beta2-Microglobulin >3 mg/l
  • Extra-nodal involvement
  • Active disease with rapid progression 5.Age from 65 to 80 years, geriatric score "FIT" (see Appendix B) 6.Life expectancy >6 months 7.ECOG performance status 0-2 (see Appendix C) 8.LVEF ≥45% or FS ≥37% 9.ANC ≥1 x 109/l and Platelets count ≥75 x 109/l, unless due to bone marrow involvement by follicular lymphoma 10.Creatinine up to 1.5 x ULN 11.Conjugated bilirubin up to 2 x ULN 12.Alkaline phosphatase and transaminases up to 2 x ULN 13.Sending of bone marrow sample for Bcl-2/IgH rearrangement evaluation 14.Written informed content

Exclusion Criteria:

• Men not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy
• History of other malignancies within 3 years prior to study entry except for: adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage, localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent
• Medical condition requiring long term use (>1 months) of systemic corticosteroids
• Active bacterial, viral, or fungal infection requiring systemic therapy 5. Concurrent medical condition which might exclude administration of therapy
• Cardiac insufficiency (NYHA grade III/IV; see Appendix D)
• Myocardial infarction within 6 months of entry on study
• Severe chronic obstructive pulmonary disease with hypoxemia
• Severe diabetes mellitus difficult to control with adequate insulin therapy
• Hypertension that is difficult to control
• Impaired renal function with creatinine clearance <30 ml/min (see Appendix E)
• HIV positivity
• HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive (these patients need to receive prophylaxis with Lamivudine)
• HCV positivity with the exception of patients with no laboratory signs of active chronic hepatitis and HCV-RNA negativity
• CNS involvement by lymphoma 16. Participation at the same time in another study in which investigational drugs are used
• Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
• Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent