"MIRO" Molecularly Oriented Immuno-radio-therapy

Inclusion Criteria:

* Histologically confirmed follicular lymphoma grade I-IIIa;
* Stage IA or IIA (no more than 2 contiguous nodal regions) non bulky (\<7 cm);
* FLIPI ≤2, FLIPI2 ≤2;
* Previously untreated;
* Age ≥ 18;
* Informed consent;
* Staging with PET-CT, bone marrow biopsy;
* Qualitative/quantitative PCR basal evaluation of Bcl-2/IgH rearranged cells in peripheral blood and bone marrow.

Exclusion Criteria:

* Follicular lymphoma grade IIIb;
* Stage greater than II with more than 2 nodal sites and/or B symptoms and/or bulky disease (\>7 cm);
* FLIPI \>2, FLIPI2 \>2;
* Age \< 18;
* Previous treatments for non-Hodgkin's lymphoma;
* Dementia;
* Impossibility to subscribe the informed consent;
* Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones or stable chronic liver disease per investigator assessment);
* Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study;
* Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible;
* Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C;
* History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae;
* Known HIV positive;
* Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to start of treatment, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities;
* Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient;
* Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a quantitative HBV-DNA test will be performed and if positive the subject will be excluded. Patients with HBcAb positivity and negative HBV DNA should be prophilactically treated with oral Lamivudine (100 mg /day) in case of treatment with Ofatumumab, to be prosecuted 12 months after treatment;
* Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HCV-RNA on the same sample to confirm the result;
* Hematologic and blood chemistry exclusion criteria:

  * platelets \<50 x 109/L;
  * neutrophils \<1.0 x 109/L;
  * creatinine \>2.0 times upper normal limit;
  * total bilirubin \>1.5 times upper normal limit;
  * ALT \>2.5 times upper normal limit;
  * alkaline phosphatase \>2.5 times upper normal limit;
* Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening:

  \- Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence;
* Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.