• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

• Age ≥ 18 years at the time of consent.

• ECOG Performance Status of 0-2 within 10 days prior to registration.

• Low grade follicular lymphoma (grade 1-2 or 3A by WHO-HAEM4R and/or cFL by WHO-HAEM5). Specifically, grade 3B or FLBL will not be allowed. Must not have evidence of transformed lymphoma at the time of study enrollment.

• Stage II, III, or IV by Ann Arbor staging system.

• Meet the definition of high tumor burden follicular lymphoma as defined by Groupe d'Etude des Lymphomes Follicularies (GELF) Criteria or be defined as high risk by the follicular lymphoma international prognostic index (FLIPI) 1 or FLIPI 2.

⁃ -GELF Criteria (Must meet ≥ 1 of the following)

⁃ Any nodal or extranodal mass ≥ 7 cm in diameter

⁃ Involvement of ≥ 3 nodal sites ≥ 3 cm

⁃ Systemic or B symptoms

⁃ Presence of serous effusion

⁃ Splenic enlargement

⁃ Risk of compression syndrome (epidural, ureteral, etc)

⁃ Leukemic phase of disease

⁃ Cytopenia deemed due to disease involvement (hemoglobin \< 10, granulocyte count \< 1.5×10\^9/L, or platelet count \< 100×10\^9/L)

• In addition to meeting GELF criteria, must have at least one FDG-avid site on PET that measures 1.5 cm in at least one dimension of a nodal site or 1cm in at least one dimension for extranodal sites.

• Received no prior therapy except local radiation therapy (field did not exceed 2 adjacent nodal regions), single agent rituximab (limited to 4 doses), or steroids for symptom control in the 28 days preceding trial enrollment.

• Must have prior EZH2 testing already performed or have tissue available to perform retrospective EZH2 testing. If prior EZH2 results are not available, tissue must be submitted. Tissue block is preferred but unstained slides are also acceptable. Patients who have insufficient or suboptimal tissue must be willing to have a biopsy performed prior to starting study drugs. See Correlative Lab Manual for details.

• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 28 days prior to registration.

‣ Hematological

• Platelets ≥ 50 K/dL

∙ Absolute Neutrophil Count (ANC) ≥ 1000 K/mm3

∙ Hemoglobin (Hgb) ≥ 8 g/dL

⁃ Renal

• Calculated creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault formula

∙ or Serum creatinine \< 2 mg/dL

⁃ Hepatic

• Bilirubin ≤ 1.5 × upper limit of normal (ULN)

∙ Aspartate aminotransferase (AST) ≤ 3 × ULN

∙ Alanine aminotransferase (ALT) ≤ 3 × ULN

⁃ Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN

• Females of childbearing potential with a male partner able to father a child must have a negative serum or urine pregnancy test within 7 days prior to registration. See the protocol for definition of childbearing potential.

• Females of childbearing potential must be willing to abstain from vaginal intercourse or use two effective methods of contraception from the time of informed consent, during the study and for 6 months after the last dose of study drug(s). Males able to father a child must be willing to abstain from vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for 3 months after the last dose of study drug(s). See the protocol.

• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.