• To evaluate the safety of bortezomib in patients with newly diagnosed multiple myeloma [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• evaluate time to disease progression following bortezomib treatment [ Time Frame: TBD ] [ Designated as safety issue: No ]
• assess the frequency and severity of peripheral neuropathy in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• To evaluate the safety of bortezomib in patients with newly diagnosed multiple myeloma
• evaluate time to disease progression following bortezomib treatment
• assess the frequency and severity of peripheral neuropathy in this patient population.

Bortezomib (Velcade) has just recently been approved by the FDA for the treatment of multiple myeloma in patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. This study will determine if Velcade is effective in treating patients with multiple myeloma that have had no prior treatment for the disease. We will also use whole-genome scanning to identify drug response biomarkers in bone marrow samples as well as nerve fiber studies to compare nerves prior to the use of Velcade and after treatment with Velcade.

• Patients will receive intravenous Velcade on a 3 week dosing cycle. Velcade will be given twice a week for 2 weeks (on days 1,4,8 and 11) followed by a 10 day rest period (days 12-21).
• On the days patients receive Velcade a physical exam, vital signs, and blood tests will be performed. A neurotoxicity-directed questionnaire will be completed once during each cycle of therapy.
• A patient may undergo up to eight 3-week dosing cycles. During the dosing phase, if after two cycles of dosing, tests indicate progressive disease the patient will be removed from the study.
• A complete response means that all traces of the disease have disappeared: there are no abnormal proteins in the blood or urine; no traces of abnormal cells in bone marrow or any other place; and no worsening of bone tumors are found. Confirmation of this will be obtained at least 6 weeks after initial testing by a bone marrow biopsy.
• An end of dosing phase visit will occur 30 days after the last study dose; or 2 dosing cycles following the time it is confirmed that there is complete response; or at the time it is confirmed that the disease has worsened.
• After the end of the study visits, patients will be asked to participate in follow-up telephone calls every 6 weeks.
• Whole-genome scanning and nerve fiber studies are optional research studies for patients enrolled in the dosing phase. The whole-genome scanning portion involves collection of a bone marrow biopsy at the start and end of the study. The nerve fiber study involves skin biopsies at the next study visit after neuropathy is reported and at the end of the study.

Inclusion Criteria:

• Diagnosis of multiple myeloma based upon standard criteria
• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1 g/dl and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours.
• Karnofsky performance status of > 60
• Hemoglobin > 8.0 g/dL
• AST (SGOT) < 3 x ULN
• ALT < 3 x ULN
• Total bilirubin < 2 x ULN
• Is infertile or is practicing an adequate form of contraception
• 18 years of age or older

Exclusion Criteria:

• Prior treatment with systemic chemotherapy
• Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes
• Plasma cell leukemia
• Calculated or measured creatinine clearance < 30 mL/minute within 14 days of enrollment
• Grade 2 or greater peripheral neuropathy
• Hypersensitivity to bortezomib, boron or mannitol
• Severe hypercalcemia
• HIV positive
• Known active hepatitis B or C
• New York Hospital Association Class III or IV heart failure
• Second malignancy requiring concurrent treatment
• Other serious medical or psychiatric illness
• Pregnant women
• Dialysis dependent patients

• Beth Israel Deaconess Medical Center
• Massachusetts General Hospital
• Brigham and Women's Hospital
• Roswell Park Cancer Institute
• Emory University
• Memorial Sloan-Kettering Cancer Center
• Millennium Pharmaceuticals, Inc.