Phase II Study of Efficacy and Safety of Lenalidomide, Subcutaneous Bortezomib and Dexamethasone Therapy for Newly Diagnosed Multiple Myeloma

Inclusion Criteria: * Diagnosis of symptomatic MM, according to International Myeloma Foundation 2003 Diagnostic Criteria: * Clonal plasma cells \>10% on bone marrow biopsy * A monoclonal protein (paraprotein) in either serum or urine(except in cases of non-secretory myeloma)\* * Myeloma-related organ dysfunction (1 or more) of the following (evidence of end-organ damage felt related to the plasma cell disorder related organ or tissue impairment (ROTI), commonly referred to by the acronym "CRAB"): * Serum Ca ≥ 10.5 mg/dL or * Renal insufficiency attributable to myeloma. Serum creatinine \> 2mg/dL * Anemia: Normochromic, normocytic with a hemoglobin value \> 2g/dL below the lower limit of normal or a hemoglobin \<10 g/dL * Bone lesions (lytic lesions, severe osteopenia or pathologic fractures) or osteoporosis. \*If no monoclonal protein is detected (non-secretory disease), then \>/= 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required. * Has received no prior treatment with any systemic therapy for the treatment of multiple myeloma * Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period). * Bisphosphonates are permitted. * Local radiation as long as two weeks have lapsed since last date of radiotherapy, which is recommended to be a limited field. * Age ≥18 years at the time of signing Informed Consent * ECOG performance status ≤ 2 (Karnofsky ≥ 50%) * Voluntary written informed consent * Subject must be able to adhere to the study visit schedule and other protocol requirements. * Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 µL/mL 10 to14 days prior to therapy and repeated again within 24 hours prior to prescribing lenalidomide for Cycle 1 and must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must practice complete abstinence or agree to use a condom during sexual contact with a FCBP even if they have had a successful vasectomy. All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program- Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. * Renal insufficiency (serum creatinine levels \> 2.5 mg/dL, calculated Crcl with Cockcroft-Gault formula, see Appendix B, \< 45 ml/min) * Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/mm3) * Subjects with an absolute neutrophil count (ANC) \< 1000 cells/mm3. Growth factors may not be used to meet ANC eligibility criteria * Subjects with a hemoglobin \< 8.0 g/dL * AST (SGOT) and ALT (SGPT) \> 2 x institutional ULN, bilirubin levels ≥1.5 institutional ULN * Concomitant therapy medications that include corticosteroids (except as indicated in inclusion criteria). * Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix C), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Clinically relevant active infection requiring treatment (antibiotics, antivirals, antifungals). * Any serious co-morbid condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. * Female subject is pregnant or breast-feeding. * Serious psychiatric illness or addiction likely to interfere with participation in this clinical study. * Uncontrolled diabetes mellitus. * Contraindication to any required concomitant drugs or supportive therapies including hypersensitivity to all anticoagulation and antiplatelet options or hypersensitivity to acyclovir or similar anti-viral drug. * History of allergic reaction/hypersensitivity attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dehydrate. * POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes). * Known seropositive for or active HIV infection or hepatitis B or C viral infection. * Patients who are seropositive because of hepatitis B virus vaccine are eligible. * Known intolerance to steroid therapy. * Patient has hypersensitivity to bortezomib, boron, or mannitol. * Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. * Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial. * Radiation therapy within 2 weeks of enrollment. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy. * Participant must be able to swallow pills.