Odronextamab in Low Tumor Volume Advanced FL

Inclusion Criteria: * Biopsy-confirmed (fresh or archival tissue) follicular lymphoma grade 1-3A that is CD20+ (by immunophenotype or immunohistochemistry) at time of diagnosis. All degrees of CD20 positivity will be accepted. * Lymph node biopsy obtained in the previous 6 months * Subjects must have measurable disease at time of enrollment as defined by at least one lymph node with long axis ≥1.5 cm * Age ≥18 years * ECOG performance status \> 2 * Life expectancy of \> 2 years * Participants must meet the following organ and marrow function as defined below: * Absolute neutrophil count ≥1000 cells/mcl * Platelets ≥100,000 cells/mcl * Hemoglobin ≥ 10 g/dL * Adequate organ function, as documented by: * Cardiac ejection fraction \>40% by echocardiogram or multi-gated acquisition (MUGA) scan * Total bilirubin ≤1.5 × upper limit of normal (ULN) (≤3 × ULN if attributed to lymphoma infiltration of liver) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if attributed to lymphoma infiltration of liver) * Alkaline phosphatase (ALP) ≤2.5 × ULN (≤5 × ULN if attributed to lymphoma infiltration of liver) * Calculated creatinine clearance by Cockcroft Gault formula ≥40 mL/min * NOTE: Irrespective of the presence of lymphoma infiltration of the liver, a participant with an AST \>3 × ULN and/or ALT \>3 × ULN concurrent with a total bilirubin \>1.5 × ULN will be excluded. * NOTE: Participants with known Gilbert syndrome will be excluded if the total bilirubin value is \>4 × ULN. * NOTE: Participants with a calculated creatinine clearance * Patients with hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible but will be required to receive appropriate antiviral prophylaxis as described in Section 5.2. Patients with Hepatitis C antibody must have undetectable viral load. * Women of childbearing potential (WOCBP)\* must agree to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose of odronextamab. Egg donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment. Highly effective contraceptive measures include: * stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening. * intrauterine device (IUD); intrauterine hormone-releasing system (IUS) * bilateral tubal ligation/occlusion * vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure) * sexual abstinence†, ‡. * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the Clinical Trial Facilitation Group guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy. * WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. * Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the assigned study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. * Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together. * WOCBP must have negative serum pregnancy test at screening. * Sexually active adult men must agree to use the following forms of medically acceptable birth control: consistent use of a condom OR vasectomy with medical assessment of surgical success, prior to initial dose, during the study and for at least 6 months following the last dose of odronextamab. Sperm donation is prohibited following odronextamab administration throughout the study and for at least 6 months following the last dose of odronextamab administration. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Participants must not meet any GELF Criteria for high tumor volume, or other circumstances for which immediate therapy would be indicated * Any nodal or extranodal tumor mass \>7 cm diameter * Involvement of at least 3 nodal sites, each with diameter \>3 cm * Presence of any systemic or B symptoms for greater than 2 weeks (fever, night sweats, or weight loss) * Splenic enlargement with inferior margin below the umbilical line * Compression syndrome (ureteral, orbital, gastrointestinal) * Pleural or peritoneal serous effusion (irrespective of cell content) * Leukemic phase (\>5.0 x10⁹/L circulating malignant cells) * Cytopenia (granulocyte count \< 1.0x10⁹/L and/or platelets \< 100x10⁹/L) * Infections: * Evidence of any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other) at study enrollment or within 2 weeks of study enrollment, if requiring ongoing treatment and/or has the potential to cause disseminated disease or severe infection upon immunosuppression. There should be evidence that the infection has cleared or is well controlled by start of study therapy. * Active symptomatic COVID-19 infection. Note, patients with prolonged PCR positivity (\>2 weeks after initial diagnosis) may be allowed to participate following discussion with the PI * Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) NOTE: Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells/μL either spontaneously or on a stable antiviral regimen) are permitted NOTE: Participants who are hepatitis B surface antigen positive or who are hepatitis B core antibody positive should undergo evaluation by a specialist and be considered to have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) before they are permitted onto study NOTE: Participants who are HCV antibody positive who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted * Another active malignancy (aside from B-cell NHL) in the past 2 years, with the following exceptions: non-melanoma skin cancer that has undergone potentially curative therapy, in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent. * Limited-stage follicular lymphoma (stage I and limited stage II) with a possibility of treatment with a curative intent using radiotherapy * Duodenal follicular lymphoma * Follicular lymphoma with spontaneous regression prior to treatment initiation * Patients who have had any prior systemic therapy for lymphoma, including rituximab and/or tazemetostat * Patients who have had prior radiation therapy, with the following exception: Low dose radiotherapy RT (2x2Gy, or 4Gy x 1) is allowed but must be completed at least 12 weeks prior to treatment on this study; patients must meet criteria for measurable/assessable disease as outlined above after completion of RT, and have a nodal evaluable disease outside the radiation area * Uncontrolled underlying cardiac conditions including but not limited to: congestive heart failure grade III or IV (by NYHA) or EF \< 45%, unstable angina pectoris, acute myocardial infarction \< 6 months, cardiac arrhythmia * History of uncontrolled neurologic condition including but not limited to: seizure disorder, stroke, psychosis, dementia, CNS vasculitis, encephalitis * Immunosuppressive therapy for non-lymphoma-related indication within 28 days of initiation of treatment, including systemic corticosteroids 10 mg/day or greater prednisone-equivalent * Patients with known or suspected CNS involvement or leptomeningeal disease are excluded * History of neurodegenerative condition or CNS movement disorder. Patients with a history seizure within 12 months prior to study enrollment are excluded. * Pregnant women or participants unwilling to adhere to institutional guidelines for highly effective contraception during odronextamab treatment and for 12 months after the last dose are excluded from this study because of documented (rituximab) and unknown risks of the treatment effect on fetal development. * Known current alcohol or drug abuse, psychiatric illness, or unstable social situation that is likely to limit compliance with study requirements * Allergy/hypersensitivity: * Known hypersensitivity to both allopurinol and rasburicase * History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biological components * Exposure to a live or a live attenuated vaccine within 4 weeks