This is a randomized phase III trial of CC-5013 (lenalidomide, NSC-703813) and low dose dexamethasone (LLD) versus bortezomib (PS-341, NSC-681239), lenalidomide and low dose dexamethasone (BLLD) for induction, in patients with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant.

1. Patients must have newly diagnosed multiple myeloma
2. Patients must have received no prior chemotherapy for this disease. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration. Patients must not have received any prior treatment with bortezomib or lenalidomide.
3. Patients must be ≥ 18 years of age at the time of registration.
4. Patients must have a Zubrod Performance Status (PS) of 0 - 3
5. Patients must have adequate marrow function as defined herein:
6. Platelet count ≥ 80 x 103/mcL,
7. ANC ≥ 1 x 103/mcL, and Hemoglobin (including patients who have been either transfused or treated with EPO) ≥ 9 g/dL.
8. Institutions must submit a local cytogenetics report and FISH analysis report
9. Patients with pathologic fractures, pneumonia at diagnosis or symptomatic hyperviscosity.
10. Patients must have a calculated or measured creatinine clearance > 30 cc/min.
11. Patients must not have uncontrolled, active infection requiring intravenous antibiotics
12. Patients must not have any psychiatric illness
13. Patients must not be Hepatitis B, Hepatitis C or HIV positive
14. Patients must not have a history of cerebral vascular accident with persistent neurologic deficits.
15. Patients must be able to take aspirin 325 mg daily
16. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
17. No prior malignancy is allowed except for 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 five years.
18. Patients must be offered participation in GEP molecular studies for the evaluation of genetic polymorphisms.