DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma (MM)

  • Stage I, II, or III disease by the New International Staging System
• Measurable disease

• Nonsecretory MM based upon standard M-component criteria (i.e., measurable serum/urine M-component) is not allowed unless the baseline serum free light chain level (Freelite™) is elevated

  • Serum Freelite must be drawn
  • No freelite chains
• Must be offered participation in the Myeloma Specimen Repository for banking and future research, and in the Gene Expression Profiling (GEP) molecular studies for the evaluation of genetic polymorphisms
• Must have baseline skeletal survey, including lateral skull, anteroposterior (AP) pelvis and posteroanterior (PA) chest within 28 days prior to study entry
• Institutions must submit a local cytogenetics report and FISH analysis prior to study entry

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-3
• Platelet count ≥ 80,000/mm³*
• ANC ≥ 1,000/mm³*
• Hemoglobin ≥ 9.0 g/dL* (including patients who have been transfused or treated with epoetin)
• Creatinine clearance > 30 cc/min
• FEV_1 and FVC ≥ 50% of predicted**
• DLCO ≥ 50% of predicted**
• No uncontrolled, active infection requiring IV antibiotics
• No NYHA class III-IV heart failure
• No myocardial infarction within the past 6 months
• No history of treatment for clinically significant ventricular cardiac arrhythmias
• No poorly controlled hypertension
• No poorly controlled diabetes mellitus
• No chronic obstructive or chronic restrictive pulmonary disease
• Must have undergone an EKG within the past month
• No psychiatric illness that could potentially interfere with the completion of study treatment
• No history of cerebral vascular accident with persistent neurologic deficits
• No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years
• No hepatitis B or C positivity
• HIV negative***
• Not pregnant or nursing
• Negative pregnancy test

• Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment

  • Female patients must use 2 reliable forms of contraception simultaneously
  • Male patients must use effective barrier contraception
• Patients with pathologic fractures, pneumonia at diagnosis, or symptomatic hyperviscosity syndrome must have these conditions attended to prior to study entry (i.e., intramedullary rod, IV antibiotics, or plasmapheresis)
• Patients must have baseline skeletal survey that include lateral skull, anteroposterior (AP) pelvis, and posteroanterior (PA) chest within the past 28 days NOTE: *Except patients with biopsy-proven heavy-marrow involvement, defined as having ≥ 30% marrow cellularity with > 50% of the cells being malignant plasma cells (documented marrow results required)

NOTE: **Patients who are unable to complete pulmonary function tests due to bone pain or fracture must undergo high resolution CT scan of the chest and have acceptable arterial blood gases, defined as P02 > 70; these tests must be completed within 42 days prior to study entry

NOTE: ***Patients with treatment-sensitive HIV infection are eligible provided immunological and virologic indices are indicative of favorable long-term survival prospects on the basis of HIV infection, but whose life expectancy is limited predominantly by multiple myeloma rather than HIV infection in the judgement of the treating physician

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for this disease
• No prior radiotherapy to a large area of the pelvis (i.e., more than half of the pelvis)
• No prior bortezomib or lenalidomide
• Prior steroid treatment allowed provided treatment was no more than 2 weeks in duration
• Must be able to take concurrent aspirin 325 mg daily (or enoxaparin 40 mg subcutaneously daily if allergic to aspirin) as prophylactic coagulation