1. Patients must be diagnosed with symptomatic Multiple Myeloma, that was symptomatic at time of initial diagnosis. For the original diagnosis of myeloma (see Appendix IV) patients should have met the following criteria at one point in their disease course:

? Bone marrow plasmacytosis with > 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma.

? Patient must have had symptomatic disease at initial diagnosis that prompted the initiation of therapy as well as evidence of end-organ damage at the time of diagnosis namely; at least one of the following: anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fracture), or renal dysfunction.

NOTE: Patients with smoldering myeloma (serum m protein >=3 gm/dL or bone marrow plasma cells =10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein <3 gm/dL and bone marrow plasma cells <10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible

2. Patients must be > 65 and have declined alternative treatment OR

Patients who are > 18 < 65 are eligible if they are not a candidate for autologous stem cell transplantation in the opinion of the treating physician.

OR have declined transplant or other alternative treatment.

3. ECOG performance status < 2.

4. All tests below must be performed within 28 days prior to randomization:

Serum free light chains

Serum M-protein by SPEP

Urine M-protein light chain excretion by UPEP NOTE: UPEP (on a 24 hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is > 200 mg/24 hr. Please note that if both serum and urine m-components are present, both must be followed in order to evaluate response.

Urine immunofixation (pos(+) or neg

Serum immunofixation (pos(+) or neg(-))

5. The following laboratory levels must be obtained within 28 days prior to randomization:

Hemoglobin > 7 g/dL

Platelet count > 75,000 cells/mm3

Absolute neutrophil count > 1000 cells/mm3.

Creatinine < 2.5 mg/dL.

Direct bilirubin < 1.5 mg/dL.

SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of normal.

6. Patients must be previously untreated for myeloma, although prior treatment for myeloma with prednisone or dexamethasone for less than 4 weeks total dosing alone or in combination with thalidomide or lenalidomide for less than 2 weeks total dosing is allowable.

7. Patients may be receiving bisphosphonates or growth factors (erythropoietin) for Multiple Myeloma. Although erythropoietin is allowed, it is strongly discouraged due to increased risk of thrombosis when employed alongside Thalidomide and/or lenalidomide therapy.

8. Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or coumadin.

9. Patients must not have uncontrolled inter-current illness that would limit compliance with the study including:

Uncontrolled hypertension

Symptomatic congestive heart failure

Unstable angina

Uncontrolled cardiac arrhythmia

Uncontrolled psychiatric illness or social situation

Prior history of Stevens Johnson Syndrome

10. Patients must not have Grade 2 or higher peripheral neuropathy.

11. Patients must not have an active, uncontrolled infection.

12. Female patients MUST NOT be pregnant or breastfeeding. Due to the potential teratogenic properties of lenalidomide and thalidomide, the use of these drugs in this patient population is ABSOLUTELY CONTRAINDICATED. For women of childbearing potential, a negative serum pregnancy test is required within 10-14 days prior to randomization. For female patients of childbearing potential a negative serum pregnancy test must be repeated within

24 hours prior to initiation of treatment, weekly for the first 4 weeks of treatment and then every 4 weeks if the patient?s periods are regular