Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone

Inclusion Criteria:

* Symptomatic multiple myeloma, that was symptomatic at time of initial diagnosis, but may be asymptomatic at the time of registration based on induction therapy
* For the original diagnosis of myeloma, patients must have met the following criteria at one point in their disease course: bone marrow plasmacytosis (\>10% plasma cells or sheets of plasma cells) or a biopsy proven plasmacytoma, and evidence of end-organ damage due to multiple myeloma including anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fractures) or renal dysfunction.
* Patients may have prior exposure to bortezomib
* Patients must have received a minimum of 1 cycle, maximum of 6 cycles, of a dexamethasone-based regimen; patient must not have experienced progressive disease on such therapy
* The following induction regimens were considered adequate for enrollment: dexamethasone alone; vincristine, doxorubicin and dexamethasone; thalidomide and dexamethasone; lenalidomide and dexamethasone; liposomal doxorubicin and dexamethasone; the combination of any of the above agents and dexamethasone; or cyclophosphamide, lenalidomide and dexamethasone
* Patients must have received the minimum cumulative dose of dexamethasone of 160 mg (sum of induction treatment) with no maximum dose specified
* Patients must have been offered and refused front-line stem cell transplant OR not have been eligible for front-line stem cell transplant.
* Bone marrow aspiration and/or biopsy must be obtained =\< 28 days prior to randomization
* All tests below must be performed =\< 28 days prior to randomization:

  * Kappa free light chain mg/dL
  * Lambda free light chain mg/dL
  * Serum M-protein by serum protein electrophoresis (SPEP)
  * Urine M-protein light chain excretion by urine protein electrophoresis (UPEP)
* Adequate laboratory levels within 7 days prior to randomization: hemoglobin \> 7 g/dL, platelet count \> 75,000 cells/mm\^3, absolute neutrophil count \> 1000 cells/mm\^3, creatinine \< 2.5 mg/dL, creatinine clearance (measured or calculated) \>= 60 mL/min, direct bilirubin =\< 1.5 mg/dL, serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.5 times the upper limit of normal
* Patients may be receiving bisphosphonates or erythropoietin growth factors (erythropoietic agents) for multiple myeloma
* Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy to date of randomization
* Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or coumadin (patients with prior deep vein thrombosis \[DVT\] are eligible provided they remain on the anticoagulation regimen that was prescribed for treatment of the DVT throughout the protocol therapy)
* Patients must be competent to understand the study as explained in the consent form
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide, and for 4 weeks after stopping treatment
* Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months
* Age \>=18 years

Exclusion Criteria:

* More than 8 weeks from the last day of last cycle of induction treatment
* Active, uncontrolled seizure disorder; seizures in the last 6 months
* Uncontrolled inter-current illness that would limit compliance with the study including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation, prior history of Stevens Johnson syndrome
* Grade 2 or higher peripheral neuropathy by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
* Active, uncontrolled infection
* Smoldering myeloma or monoclonal gammopathy of undetermined significance
* Pregnant or nursing women were not eligible. Women of child-bearing potential unwilling to use a dual method of contraception and men who were unwilling to use a condom were not eligible