The purpose of this research is to estimate the effectiveness of a response adapted approach with the use of the drug, lenalidomide in the treatment of older adults with newly diagnosed standard risk multiple myeloma. This means that participants will be given the study drug, lenalidomide but depending on how they respond to this drug they may also be given dexamethasone and/or prednisone to help with their treatment.

Summary: Patients will be started on the study drug, lenalidomide on Day 1, Cycle 1. Lenalidomide is a capsule that is to be taken orally (by mouth). If the patient's disease progresses after 2 cycles of therapy, a low dose of dexamethasone will be added. If the patient's disease is stable after 2 cycles of therapy, the use of an alternate corticosteroid (prednisone) will be added to the lenalidomide therapy they are receiving. Dexamethasone and prednisone are in tablet form and will be taken orally (by mouth). However, if the patient has a minimal response after an additional 2 cycles of lenalidomide therapy, the therapy will be continued until their disease progresses. See the intervention descriptions for further details.

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form
• Age ≥65 years or not eligible for high dose therapy and autologous stem cell transplant
• Able to adhere to study visit schedule and other protocol requirements
• Diagnosed with multiple myeloma and considered to have active disease. Patients must not have received an active chemotherapy regimen or Dexamethasone. Patients may have received palliative radiotherapy at least 2 weeks prior to the study start.
• Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL), urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by serum free light chains (involved free light chain greater than 100mg/L)
• Eastern Cooperative Group (ECOG) Performance Status of 0 or 1
• Serum bilirubin levels ≤1.5 times the upper limit of the normal (ULN) range for the laboratory
• Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) levels ≤2 x ULN
• Adequate bone marrow function: Absolute neutrophil count ≥ 1,000 cells/mm³ (1.0 x 10^9/L); Platelets ≥ 100,000 /mm³
• Hemoglobin > 8 g/dL
• Adequate renal function: Calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula
• Low risk myeloma is defined as the absence of the following adverse features[21]: t(4;14) by FISH or metaphase cytogenetics; t(14,16) or t(14;20) by FISH or metaphase cytogenetics; Deletion 17q13 by FISH; Deletion 13 by metaphase analysis; Aneuploidy by metaphase analysis; Β2 microglobulin > 5.5.
• Able to tolerate one of the following thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin (coumadin)
• Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU/mL) within 10 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy.

Exclusion Criteria:

• Ongoing severe infection requiring intravenous antibiotic treatment
• Life expectancy of less than 3 months
• Performance status of 2, 3 or 4
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the patient has been disease-free for at least 2 years
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
• Uncontrolled medical problems such as diabetes mellitus, congestive heart failure, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or lactating
• Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Known hypersensitivity to thalidomide
• Use of any other experimental drug or therapy within 28 days of baseline.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Any prior use of lenalidomide
• Concurrent use of other anti-cancer agents or treatments
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.

Adverse Events collected from consent through off treatment date, an average of 24 months. Serious Adverse events collected from consent to off-study date, an average of 48 months