Bortezomib, Cyclophosphamide, Dexamethasone, and Thalidomide in Treating Patients With Newly Diagnosed, Previously Untreated Multiple Myeloma

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma meeting 1 of the following criteria:
• Monoclonal immunoglobulin spike on serum electrophoresis (IgG > 3.5 g/dL or IgA > 2.0 g/dL) and kappa or lambda light chain excretion > 1 g/day by 24-hour urine protein electrophoresis AND meets any of the following criteria:
• Bone marrow plasmacytosis (10-30% plasma cells)
• Lytic bone lesions
• Monoclonal immunoglobulin of lesser magnitude present and bone marrow plasmacytosis (10-30% plasma cells) AND meets any of the following criteria:
• Lytic bone lesions
• IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
• Bone marrow plasmacytosis (> 30% plasma cells) or plasmacytoma on tissue biopsy AND meets any of the following criteria:
• Monoclonal immunoglobulin of lesser magnitude present
• Lytic bone lesions
• IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL
• FreeLite testing abnormal and kappa:lambda light chain ratio abnormal
• Symptomatic disease requiring treatment
• Documented related organ or tissue involvement, if present
• Measurable disease, defined as 1 of the following:
• Monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/day
• Abnormal FreeLite testing (for nonsecretors)
• Patients with nonsecretory disease must meet either of the following criteria for measurability:
• Has measurable protein by FreeLite testing
• Untreated soft tissue plasmacytoma and/or evaluable disease in bone marrow
• Newly diagnosed, previously untreated disease
• No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
• No plasma cell leukemia

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%
• Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ if bone marrow is extensively infiltrated)
• Extensive infiltration is defined as > 50% myeloma cells or plasma cells
• Hemoglobin ≥ 8.5 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• AST and ALT ≤ 2 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN (unless clearly related to the disease)
• Creatinine clearance ≥ 20 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 methods of effective contraception ≥ 4 weeks prior to beginning treatment, during, and for ≥ 4 weeks after completion of study treatment
• No impaired kidney function requiring dialysis
• No uncontrolled infection
• No HIV positivity
• No known active hepatitis B or C
• No cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction within the past 6 months
• New York Heart Association class II-IV heart failure
• Uncontrolled angina
• Severe uncontrolled ventricular arrhythmias
• Clinically significant pericardial disease
• Acute ischemic or active conduction system abnormalities by EKG
• No history of allergic reactions to compounds containing mannitol, bortezomib, or cyclophosphamide
• No second malignancy requiring concurrent treatment
• No other serious medical or psychiatric illness that would preclude study compliance
• No peripheral neuropathy ≥ grade 1

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, immunotherapy, vaccine therapy, therapeutic doses of steroids, or other agents for the treatment of active myeloma
• Drugs given to prevent onset of myeloma allowed
• Bisphosphonates for hypercalcemia or short course corticosteroids for hypercalcemia or cord compromise allowed
• Prior local radiotherapy with or without a brief exposure to steroids allowed
• More than 4 weeks since prior and no concurrent radiotherapy
• Spot radiotherapy to ≤ 3 vertebrae allowed
• No concurrent steroids at > 10 mg of prednisone daily (or the equivalent) for other medical conditions (e.g., asthma, systemic lupus erythematosus, or rheumatoid arthritis)
• No other concurrent chemotherapy or investigational agents
• Concurrent daily acetylsalicylic acid required during course 4-6 of study treatment