Inclusion Criteria:

• Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a measurable CNS lesion (≥ 1 cm in largest dimension); NOTE: tissue biopsy is not absolutely necessary unless clinical findings strongly suggest other etiologies as per treating physician; initial diagnosis must be made by tissue biopsy.
• Relapsed/refractory primary vitreoretinal DLBCL who also have a measureable CNS lesion ≥ 1 cm in largest dimension); NOTE: tissue biopsy requirement of the CNS lesion is as outlined in bullet above; ocular tissue biopsy is required if ophthalmologic examination findings indicate ocular relapse.
• Newly diagnosed or relapsed/refractory primary vitreoretinal DLBCL with or without cerebrospinal fluid (CSF) involvement but without brain or spinal cord involvement; NOTE: ocular tissue biopsy is required for all cases as part of ophthalmologic examination; Note: these patients will be eligible for participation in MTD expanded phase of the study.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
• Absolute neutrophil count (ANC) ≥ 1000/uL
• Platelets (PLT) ≥ 100,000/uL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN the direct bilirubin must be ≤ 1.5 x ULN (≤ 0.45 mg/dL)
• Aspartate aminotransferase (AST) ≤ 3 x ULN
• Creatinine ≤ 2.5 x ULN
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting Pomalidomide and must either commit to continued 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; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or heparin)
• Provide informed written consent
• Willing to return to participating medical institutions for follow-up

Exclusion Criteria:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Uncontrolled infection
• Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration; Note: unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol
• Persistent toxicities ≥ grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment
• History of thromboembolic episodes ≤ 3 months prior to registration
• 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)
• Immunodeficiency states including human immunodeficiency virus (HIV) infection
• Active hepatitis B or C with uncontrolled disease; Note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients hepatitis B core immunoglobulin M antibody (HBcIgM Ab), hepatitis B surface antigen (HBsAg) and hepatitis C antibody screen (HCV Ab Scrn) w/Reflex testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B (HBV) infection
• Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
• Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications
• Any severe and/or uncontrolled medical conditions or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study
• Major surgery ≤ 4 weeks prior to registration or have not recovered from side effects of such therapy
• New York Heart Association classification III or IV