Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (\> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass \>= 7 cm in any uni-dimensional measurement) stage II

* Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable for diagnosis

* Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation

Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression

Low or intermediate risk by Follicular Lymphoma International Prognostic Index (FLIPI): 0-2 risk factors

No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy); patients may have received involved-field radiation therapy

No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease

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

Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass \> 1 cm is acceptable

* Lesions that are considered non-measurable include the following:

* Bone lesions (lesions if present should be noted)

* Ascites

* Pleural/pericardial effusion

* Lymphangitis cutis/pulmonis

* Bone marrow (involvement by NHL should be noted)

No known central nervous system (CNS) involvement by lymphoma

Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following

* No evidence of coinfection with hepatitis B or C

* CD4+ cell count \>= 400/mm\^3

* No evidence of resistant strains of HIV

* If not on anti-HIV therapy, HIV viral load \< 10,000 copies HIV RNA/mL

* If on anti-HIV therapy, HIV viral load \< 50 copies HIV RNA/mL

* No history of acquired immune deficiency syndrome (AIDS)-defining conditions

What this study is about