Pomalidomide in Treating Patients With Relapsed or Refractory Waldenstrom Macroglobulinemia

• Understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Waldenstrom's macroglobulinemia that has relapsed and/or is refractory to at least one prior line of therapy
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry
• Serum creatinine =\< 2.0 mg/dL
• Creatinine clearance >= 45 ml/min
• Total bilirubin =\< 3 x upper limit of normal (ULN) or direct bilirubin =\< 2 x ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =\< 2 x ULN
• Platelet count >= 20 K/microL
• Absolute neutrophil count >= 500 K/microL
• Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
• 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 to 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 practice complete abstinence or agree use a latex condom during sexual contact with a FCBP while participating in the study, during dose interruptions and for at least 90 days following study drug discontinuation, even if they have had a successful 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 (325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use therapeutic dose warfarin or low molecular weight heparin)
• All study participants must be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking pomalidomide or for 28 days after stopping pomalidomide)
• Any medical or psychiatric condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, or confounds the ability to interpret data from the study
• Use of any other experimental drug or therapy within 28 days of the first dose of study drug
• Known hypersensitivity to thalidomide or lenalidomide
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Any prior use of pomalidomide
• Concurrent use of other anti-cancer agents or treatments
• Known positive for human immunodeficiency virus (HIV) or acute hepatitis A or acute or chronic active hepatitis B or C
• Grade > 2 peripheral neuropathy
• Neutrophil count \< 1000 K/microL and/or
• Platelet count \< 100 K/microL unless infiltration by Waldenström's macroglobulinemia equals or exceed 60% of bone marrow cellularity