RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and dexamethasone work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide and dexamethasone together with bortezomib may kill more cancer cells.

PURPOSE: This phase II trial is studying giving cyclophosphamide and dexamethasone together with bortezomib to see how well it works in treating patients with newly diagnosed multiple myeloma.

OBJECTIVES:

Primary

* To evaluate the response rate (complete response [CR], near CR [nCR], and very good partial response) in patients with newly diagnosed multiple myeloma treated with bortezomib in combination with cyclophosphamide and dexamethasone .

Secondary

• Determine the overall response rate (partial response, PR, or better) in these patients after 4, 8, and 12 courses of this regimen.
• Determine the duration of progression-free and overall survival of patients treated with this regimen.
• To evaluate the toxicity of this regimen in these patients.
• To evaluate the ability to successfully collect peripheral blood stem cells from these patients after 4 months of this regimen.
• To evaluate the CR or nCR rate in these patients after 8 and 12 courses of this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral cyclophosphamide on days 1, 8, 15, and 22; bortezomib IV on days 1, 4, 8 , and 11 OR days 1, 8, 15 and 22; and dexamethasone on days 1-4, 9-12, and 17-20 in courses 1 and 2 and days 1, 18, 15, and 22 in all subsequent courses. Courses repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of symptomatic multiple myeloma

  • Durie Salmon stage 2 or higher
  • Previously untreated multiple myeloma (including immunomodulatory drugs such as thalidomide) with the exception of bisphosphonates

• Evaluable or measurable disease, as defined by at least one of the following:

  • Serum monoclonal protein ≥ 1 g/dL (measurable disease)
  • Urine monoclonal protein ≥ 200 mg/24 hours by protein electrophoresis (measurable disease)
  • Serum-free light chains (FLC) ≥ 10 mg/dL, kappa or lambda, accompanied by an abnormal kappa/lambda ratio

Serum FLC's should only be used for patients without measurable serum or urine m-spike

- Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

* Patients diagnosed with smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2

  - ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator

• Total bilirubin normal OR direct bilirubin ≤ 2.0 mg/dL

• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)

• AST ≤ 3 times ULN

• Creatinine ≤ 3.5 mg/dL

• Absolute neutrophil count ≥ 1,000/mm³ without transfusion or growth factor

• Platelet count ≥ 100,000/mm³ without transfusion or growth factor

• Willingness and the physical and mental capability to provide written informed consent

• Willingness to return to Mayo Clinic Arizona/Princess Margaret Hospital for follow-up

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

Exclusion criteria:

• Peripheral sensory neuropathy ≥ grade 2 as defined by National Cancer Institute (NCI) Common Terminology for Common Adverse Events (CTCAE) version 3.0

• Known hypersensitivity to compounds containing boron or mannitol

• Active uncontrolled infection

• Severe cardiac comorbidity including but not limited to:

  • New York Heart Association class III or IV heart failure
  • History of myocardial infarction within the past 6 months
  • Uncontrolled angina or electrocardiographic (ECG) evidence of acute ischemia
  • Severe uncontrolled ventricular arrhythmias or ECG evidence of active conduction system abnormalities
  • Cardiac amyloidosis with hypotension (i.e., systolic blood pressure < 100 mm Hg)

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent study compliance or completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Prior high-dose corticosteroid therapy for 12 days or less is permitted for emergent complications from newly diagnosed multiple myeloma

• More than 14 days since prior investigational agents

• No concurrent steroids or any other anticancer agents or treatments

  - Patients may receive the equivalent of up to 20 mg prednisone per day for concurrent illness or adrenal replacement therapy

• Concurrent palliative radiotherapy for bony pain or fracture is allowed