Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma

Inclusion Criteria: 1. Patients must have a histologically-confirmed diagnosis of follicular non-Hodgkin's B-cell lymphoma, grade 1-2 (grade 1 or grade 2 by WHO classification prior to 2009). 2. Patients must have Ann Arbor Stage III or IV extent of disease after complete staging. 3. Patients must have a willingness and ability to follow prescribed radiation precautions 4. Patients must not have had any previous treatment for low-grade lymphoma including chemotherapy or radiation. They may be newly diagnosed or observed without treatment after diagnosis. Symptomatic and asymptomatic patients will be eligible. 5. Patients must have a performance status of 0-2 on the Eastern Cancer Oncology Group (ECOG) scale and an anticipated survival of at least 3 months. 6. Patients must have an absolute neutrophil count \>1500 cells/mm3 and a platelet count \>100,000 cells/mm3 within 14 days of study entry. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products. 7. Patients must have adequate renal function (defined as serum creatinine \<2.0) and hepatic function (defined as total bilirubin \<1.5 x ULN and Aspartate Aminotransferase (AST) \<3 x ULN) within 14 days of study entry. 8. Patients must have bi-dimensionally measurable disease. Exclusion Criteria: 1. Patients with follicular Grade 3a or 3b by WHO Classification. 2. Patients with evidence of active infection requiring IV antibiotics at the time of study entry. 3. Patients with New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation. 4. Patients with active obstructive hydronephrosis. 5. Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years. 6. Patients with known HIV infection. 7. Patients with known brain or leptomeningeal metastases. 8. Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test within 7 days of study entry and methotrexate is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy. 9. Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials. 10. Patients with previous allergic reactions to methotrexate. 11. Patients who were previously given any monoclonal antibody, regardless of species, for any condition. 12. Detectable serum levels of HAMA. 13. Patients who are concurrently receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.