Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma

Patient must have one of the following:

* Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a brain lesion \>= 1 cm, or with cerebrospinal fluid (CSF) relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy

* NOTE: Tissue biopsy is not absolutely necessary for brain tumor unless clinical and radiologic findings strongly suggest other etiologies as per treating physician. Initial diagnosis must be made by tissue biopsy OR

* Relapsed/refractory primary vitreoretinal diffuse large B cell lymphoma (DLBCL) with a CNS lesion \>= 1 cm, or with CSF relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy. Relapsed PVRL must have progressed or failed at least one systemic regimen

* NOTE: Intraocular treatments are not regarded as systemic therapy

* NOTE: If recurrence in ocular or leptomeningeal space, the patient will need a positive ocular tissue biopsy and CSF biopsy. Tissue biopsy requirement of the CNS lesion is as outlined in bullet above

Patient progressed after or did not respond to at least 1 line of systemic therapy (e.g., high-dose methotrexate, high-dose methotrexate based regimen, high dose cytarabine, etc)

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3

Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within =\< 14 days prior to registration)

Platelet count \>= 100,000/mm\^3 (within =\< 14 days prior to registration)

Hemoglobin \>= 9.0 g/dL (within =\< 14 days prior to registration)

Direct bilirubin \< 1.5 x upper limit of normal (ULN) (or total bilirubin =\< 3.0 x ULN with direct bilirubin =\< 1.5 x ULN in patients with well-documented Gilbert?s Syndrome) (within =\< 14 days prior to registration)

Aspartate transaminase (AST) =\< 3 x ULN (within =\< 14 days prior to registration)

Creatinine =\< 1.5 x ULN OR calculated creatinine clearance must be \>= 45 ml/min using the Cockcroft-Gault formula (within =\< 14 days prior to registration)

Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of anticoagulants (within =\< 14 days prior to registration)

Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/ml, =\< 14 days prior to registration and within 24 hours of starting pomalidomide. In addition, must either commit to continue abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. WOCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a WOCBP even if they have had a vasectomy. In addition, women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

* A woman of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Able to take aspirin (81 or 325 mg) daily or an anticoagulant (as determined by treating physician) as prophylactic anticoagulation

Provide written informed consent

Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Willingness to undergo biopsy procedures, if deemed necessary by treating physician

Willing to be registered into a mandatory POMALYST REMS program, and willing and able to comply with the requirements of the POMALYST REMS program

Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma

What this study is about

Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma

What this study is about