• A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated

• Able and willing to provide written informed consent and to comply with the study protocol

• Bi-dimensionally measurable disease, with at least one mass lesion \>= 2 cm in longest diameter by CT, PET/CT, and/or magnetic resonance imaging (MRI)

• Must be in need of therapy as evidenced by at least one of the following criteria:

‣ Bulky disease defined as:

• A nodal or extranodal (except spleen) mass \> 7 cm in its greater diameter or,

∙ At least 3 nodal or extranodal sites \>= 3 cm in diameter

⁃ Presence of at least one B symptom:

• Fever (\> 38 Celsius \[C\]) not due to infectious etiology

∙ Night sweats

∙ Weight loss \> 10% in the past 6 months

⁃ Fatigue due to lymphoma

⁃ Splenomegaly (\> 13 cm)

⁃ Compression syndrome (ureteral, orbital, gastrointestinal)

⁃ Any of the following cytopenias, due to lymphoma:

• Hemoglobin =\< 10 g/dL

∙ Platelets =\< 100 x 10\^9/L

∙ Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L

⁃ Pleural or peritoneal effusion

⁃ Lactate dehydrogenase (LDH) \> upper limit of normal (ULN) or beta (B)2 microglobulin \> ULN

⁃ Other lymphoma-mediated symptoms as determined by the treating physician

• Stage II, III, or IV disease

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2

• Absolute neutrophil count (ANC) \> 1.0 x 10\^9/L

• Platelet count \> 50 x 10\^9/L

• Prothrombin time (PT)/international normal ratio (INR) \< 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) \< 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonists, then INR =\< 3.0)

• Serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x upper limit of normal (ULN)

• Creatinine clearance \> 30 ml/min calculated by modified Cockcroft-Gault formula

• Bilirubin \< 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL

• Women of childbearing potential and men who are sexually active must practice reliable contraceptive measures started at least 4 weeks before study therapy and continued for 18 months following discontinuation of therapy. Females of childbearing potential must either completely abstain from heterosexual sexual contact or must use 2 methods of reliable contraception. Reliable contraceptive methods include 1 highly effective method (intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants) and at least 1 additional method (condom, diaphragm, or cervical cap) every time they have sex with a male. Males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential. Men must agree to not donate sperm during and for 90 days after the last dose of study drug

• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[B-hCG\]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study

• Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study