Study to Evaluate the Efficacy of Response-adapted Strategy in Follicular Lymphoma

This is a multicenter, randomized, phase III, superiority study comparing standard vs response driven approach to maintenance. Adult patients (age ≥ 18 years) with naïve, untreated follicular lymphoma, stage II-IV, Follicular Lymphoma International Prognostic Index 2 (FLIPI2) \>0 requiring a therapeutic intervention will be recruited and randomly assigned in a 1:1 ratio to either standard or experimental arm. All patients will receive the same induction therapy with 6 cycles of R-CHOP or R-bendamustine and 2 additional doses of Rituximab. At baseline patients will be assessed for molecular status and staged by means of CT scan. A baselineFluorine-18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scan should also be performed. At the end of chemoimmunotherapy all patients will be assessed for disease response by common clinical and laboratory examination, CT scan and FDG-PET. An intermediate assessment of response with CT scan and FDG-PET (optional) will also be performed after the first four courses of R-chemoimmunotherapy. At the end of induction therapy the status of minimal residual disease will be also evaluated. After induction treatment all responding patients in the standard arm will receive standard maintenance therapy with Rituximab (every 2 months for 2 years), while patients in the experimental arm will be subdivided into two risk groups and assigned to different post induction treatments based on FDG-PET and MRD results. In both arms, patients with stable or progressive disease (PET positive and less than PR on CT scan) will be addressed to salvage treatment chosen at physician discretion. In the experimental arm, risk group allocation will be performed primarily on the basis of FDG-PET results: * Group 1 (low risk): negative FDG-PET * Group 2 (high risk): positive FDG-PET Patients at low risk (FDG-PET negative) will received maintenance therapy according to their MRD status,particularly: * Group 1a (MRD negative): observation * Group 1b (MRD positive): pre-emptive Rituximab therapy Patient at high risk (FDG-PET positive) will receive maintenance regardless of their MRD status: · Group 2: intensified maintenance ((90)Y Ibritumomab Tiuxetan + Rituximab maintenance )