Ofatumumab and Bortezomib in Treating Patients With Previously Untreated Waldenstrom Macroglobulinemia

Inclusion Criteria:

* Diagnosis of Waldenstrom Macroglobulinemia and presence of cluster of differentiation (CD)20+ tumor cells as determined by immune-histochemistry or flow cytometric analysis in bone marrow or representative lymphoid tissue specimen; to be deemed eligible, patients must meet at least one of the following criteria:

  * Rising immunoglobulin (Ig)M
  * Hemoglobin =\< 10 g/dL
  * Platelet count =\< 100 x 10\^9/L
  * Symptomatic or bulky lymphadenopathy or organomegaly
  * Systemic manifestations of Waldenstrom Macroglobulinemia (WM), such as hyperviscosity symptoms (patients with symptoms of hyperviscosity syndrome must be treated with plasmapheresis to control the syndrome prior to enrollment), neuropathy, amyloidosis, cryoglobulinemia, B-symptoms, or recurrent bleeding
* Must have a measurable disease as defined by the monoclonal IgM level of 1 g/dL on serum protein electrophoresis (SPEP); if the level of IgM on SPEP is less than 1 g/dL in patients who meet any criteria in inclusion criteria 2, then the IgM level obtained from nephelometric measurement may be used to justify this criterion
* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 2
* Have a life expectancy of \>= 3 months
* Absolute neutrophil count \>= 1.0 x 10\^9/L unless the result of disease infiltration of bone marrow
* Platelet count \>= 50 x 10\^9/L unless the result of disease infiltration of bone marrow
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x the institutional upper limit of normal (ULN)
* Total bilirubin =\< 3 mg/dL or 1.5 x institutional ULN, whichever is lower
* Serum creatinine =\< 3 mg/dL
* Female patients are either post-menopausal or surgically sterilized otherwise they must agree to use acceptable contraceptive methods (e.g. double barrier) during treatment
* Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to one of the following:

  * Practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug
  * Completely abstain from heterosexual intercourse
* Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent prior to receiving any study related procedure

Exclusion Criteria:

* Pregnant and nursing female patients
* Prior anti-neoplastic therapy for WM; the use of plasmapheresis to manage the symptoms of hyperviscosity and other IgM paraprotein mediated symptoms is allowed and does not disqualify a patient from the study; if a patient undergoes plasmapheresis within 8 weeks of starting the study treatment then the IgM level prior to plasmapheresis should be used for response assessment; neoplastic use of glucocorticoids is prohibited during the screening and treatment period; patients with active hyperviscosity symptoms should not be enrolled in this study unless the symptoms resolve after plasmapheresis
* Unwilling or unable to follow protocol requirements
* Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
* Received an investigational agent within 30 days prior to enrollment
* Known human immunodeficiency virus (HIV) positive
* Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if HBsAg is negative and hepatitis B core antibody (HBcAb) is positive, regardless of hepatitis B surface antibody (HBsAb) status, a HB deoxyribonucleic acid test will be performed and if HB DNA is positive the patient will be excluded; if a patient is HBsAg negative, HBcAb positive, and HBsAb positive, indicating past but not active infection, the patient will be included on the study
* Positive serology for hepatitis C (HC) defined as a positive test for Hep C by enzyme immunoassays (EIA), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result
* Diagnosis of a malignant disorder other than WM within 3 years of the study enrollment with the exception of completely resected non-melanoma skin cancer and successfully treated in-situ cancer
* Uncontrolled infection
* Hypersensitivity to bortezomib, boron, or mannitol
* Grade 2 or greater peripheral neuropathy; since WM is known to cause peripheral neuropathy (PN), if, in investigator's judgement, a patient has Grade 2 PN related to WM, then he/she can be enrolled onto the study; under no circumstances patient with greater than Grade 2 PN can be enrolled
* Myocardial infarction within 6 months of enrollment; New York Heart Association (NYHA) Class III or more heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias; arrhythmias requiring active therapy other than chronic stable atrial fibrillation; if a patient has an implanted cardiac pacemaker and is otherwise well can be enrolled onto this study after demonstrating normal ejection fraction and clearance from a cardiologist; at the time of screening any electrocardiographic abnormality has to be documented as not medically relevant by the investigator before the patient proceeds to the enrollment phase
* Any serious medical or psychiatric illness that may interfere with participation in the study
* Patients with symptoms of hyperviscosity syndrome will not be enrolled on the study until they undergo plasmapheresis that results in resolution of symptoms and optimal control of the syndrome