Inclusion Criteria:

- 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

- 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

- 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