MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

Inclusion Criteria:

* Histologic proof of recurring or residual follicular B-cell non-Hodgkin's lymphoma (grade I or II), by Revised European American Lymphoma Classification (REAL) or World Health Organization (WHO) classifications which has relapsed or persisted after 3 or fewer conventional therapies, including chemotherapy or monoclonal antibody therapy; note: all patients with previously treated B-cell lymphomas of any histology with the exception of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) are eligible
* Tumor measurable by computed tomography (CT) scans (at least one pathologic node measuring 2.0 x 2.0 cm, or 2 nodes measuring \> 1.5 x 1.5 cm after collection of tumor for immunologic analyses)
* At least one prior treatment regimen but no more than 3 prior chemotherapy regimens; patients previously treated with monoclonal antibodies or radiotherapy to a single site will be eligible; these therapies will be considered prior treatment regimens but will not be considered as prior chemotherapy; tumor vaccines will not be counted as prior therapies, as all such agents are investigational
* Absolute neutrophil count (ANC) \>= 1000/uL
* Platelets (PLT) \>= 75,000/uL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) =\< 3 x upper limit or normal (ULN)
* Creatinine =\< 1.5 x ULN
* Hemoglobin \>= 8 g/dL
* Ability to provide informed consent
* Willingness to return to the Mayo Clinic Rochester or the University of California, Los Angeles for follow up
* Life expectancy \>= 24 weeks
* Willingness to provide all biologic specimens as required by the protocol

Exclusion Criteria:

* Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4
* Any uncontrolled infection, hepatitis C virus (HCV)+ (unless HCV ribonucleic acid \[RNA\]-negative by polymerase chain reaction \[PCR\]) or hepatitis B surface antigen (HBsAg)+, or human immunodeficiency virus (HIV) positive patients or patients with known immune deficiency states
* Previous MDX-010 therapy regardless of interval since last treatment
* Prior treatment with fludarabine or 2-chlorodeoxyadenosine =\< 12 months prior to registration
* Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
* New York Heart Association classification III or IV or a history of angina pectoris requiring active treatment
* Clinical evidence of central nervous system involvement by lymphoma
* Any of the following:

  * Pregnant women
  * Nursing women
  * Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], or abstinence, etc.)
* Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration \[FDA\]-approved indication and in the context of a research investigation)
* Diagnosis of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL)
* Any requirement for concurrent steroid therapy, including use of inhaled steroids for asthma
* History of autoimmune disease requiring systemic therapy with immunosuppressive drugs, including but not limited to rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, or psoriasis
* Antinuclear antibody (ANA) titer or rheumatoid factor titer \> 3x institutional ULN