PRIMARY OBJECTIVES: I. To evaluate the response rate to PS-341 (bortezomib) induction in patients with high risk, newly diagnosed multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate progression free survival. II. To explore the response rate of patients who relapse or progress on maintenance and then return to induction schedule. III. To explore duration of second response. TERTIARY OBJECTIVES: I. To explore a possible differential response to PS-341 with previously described adverse prognostic indicators. II. To explore specific gene expression profiles (GEP) that may predict response to therapy to an agent or combination of agents used in the treatment of newly diagnosed myeloma. III. To explore specific post-treatment gene expression profiles (GEP) in the patients who have received 4 cycles of therapy and achieved a minimal response or better. IV. To develop relevant information about the immune system for multiple myeloma patients treated with PS-341. OUTLINE: INDUCTION TREATMENT: Patients receive bortezomib intravenously (IV) on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE TREATMENT: Patients who complete induction treatment without progressive disease receive bortezomib IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. REINDUCTION TREATMENT: Patients who progress while on maintenance treatment receive bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 4 years.
Inclusion Criteria: * Patients must not have received prior myeloma specific therapy (chemotherapy, radiotherapy, or biologic therapy) other than bisphosphonate therapy * Patients may have received radiation of plasmacytoma (for example, solitary plasmacytoma); the last such treatment must have occurred \>= 4 weeks prior to registration * Patients must be recently diagnosed with symptomatic multiple myeloma confirmed by meeting one or more of the following criteria (obtained =\< 30 days prior to registration): * NOTE: serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP) and marrow biopsy all must be done at baseline in order to evaluate response * Monoclonal protein in the serum \>= 1 g/dl (measurable disease), or * Monoclonal light chain in the urine protein electrophoresis \>= 200 mg/24 hours (measurable disease), or * Bone marrow plasmacytosis \>= 30% without either of the values in above (evaluable disease) * Patients must meet one or more of the following (all tests must be been drawn =\< 30 days prior to registration but all results are not required to be available at time of registration as long as at least one of the following criteria has been met; if patient is otherwise eligible, plasma cell labeling index \[PCLI\] is not required, but is requested): * Beta-2 microglobulin \>= 5.5 mcg/mL, or * PCLI \>= 1, or * Deletion 13 by cytogenetics * Platelet count \>= 20,000/mm\^3, with or without transfusion support * Hemoglobin \>= 7.0 g/dL, with or without transfusion support * Absolute neutrophil count (ANC) \>= 500/mm\^3 without growth factor support * Direct bilirubin within =\< 1.5 x upper normal limits (UNL) * Alkaline phosphatase =\< 2.5 x UNL * Aspartate aminotransferase (AST) =\< 2.5 x UNL * Calculated or measured creatinine clearance \>= 20 mL/minute * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2; exception: PS = 3 if secondary to acute bone event (fracture) * Patients may not receive concurrent chemotherapy, radiotherapy or biologic therapy while on study; the exception for corticosteroids is made for those taking chronic corticosteroids for disorders other than myeloma, such as rheumatoid arthritis, adrenal insufficiency, etc. * NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment * Patients must not have a history of allergic reaction attributable to compounds containing boron or mannitol * Patient must not have a peripheral neuropathy \> grade 1, as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 3.0): * Grade 2: Objective sensory (or motor) loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living (ADL) * Grade 3: Sensory (or motor) loss or paresthesia interfering with ADL * Grade 4: Permanent sensory (or motor) loss that interferes with function * Patient must be capable of understanding the investigational nature, potential risks and benefits of the study * Patient must have adequate cardiac function; patient must not have: * History of a myocardial infarction within 6 months of enrollment * New York Heart Association (NYHA) class III or IV heart failure * Uncontrolled angina or electrocardiographic evidence of acute ischemia * Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities * Cardiac amyloidosis * Patient must not have any other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol * Patient must not have poorly controlled hypertension * Women must not be pregnant or breast feeding; all females of childbearing potential must have a blood test or urine study within 7 days prior to registration to rule out pregnancy * Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
is designated in this study