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