The following criteria is provided for health care professionals.

Inclusion Criteria:

• STEP I: Patients must be diagnosed with symptomatic standard-risk multiple myeloma (SR-MM) as defined by all of the following:
  • No evidence of t(4;14), t(14;16),t(14;20), or deletion 17p on fluorescent in situ hybridization (FISH)
  • Standard risk gene expression profile (GEP)70 signature (only if GEP has been done and results are available)
  • Serum lactate dehydrogenase (LDH) =< 2 x upper limit of normal (ULN)
  • No more than 20% circulating plasma cells on white blood cell (WBC) differential or 2,000 plasma cells/microliter of peripheral blood
• STEP I: Patients must have measurable or evaluable disease as defined by having one or more of the following:
  • >= 1g/dL monoclonal protein (M-protein) on serum protein electrophoresis
  • >= 200 mg/24 hrs of monoclonal protein on a 24 hour urine protein electrophoresis
  • Involved free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
  • Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
  • Serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chain (FLC) assay, or bone marrow biopsy and or aspirate are required to be performed within 28 days prior to randomization
    • 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
    • NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine; measurable disease in the serum is defined as having a serum M-spike >= 1 g/dL; measurable disease in the urine is defined as having a urine M-spike >= 200mg/24 hr
• STEP I: Hemoglobin >= 8 g/dL
• STEP I: Untransfused platelet count >= 75,000 cells/mm^3
• STEP I: Absolute neutrophil count >= 1000 cells/mm^3
• STEP I: Calculated creatinine clearance >= 30 mL/min
• STEP I: Bilirubin =< 1.5 mg/dL
• STEP I: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) < 2.5 times the upper limit of normal
• STEP I: Patients must have received no more than one cycle (4 weeks or less) of prior chemotherapy and no more than 160mg of prior dexamethasone for treatment of symptomatic myeloma; they should not have been exposed to lenalidomide, bortezomib or carfilzomib for treatment of symptomatic myeloma; prior radiation therapy to symptomatic lesions is allowed provided 14 days have elapsed from the completion of radiation therapy
• STEP I: Prior systemic glucocorticoid use for the treatment of non-malignant disorders is permitted; prior or concurrent topical or localized glucocorticoid therapy to treat non-malignant comorbid disorders is permitted; note: concurrent use after registration on the study should be restricted to the equivalent of prednisone 10 mg per day
• STEP I: Patients must not have active, uncontrolled seizure disorder; patients must have had no seizures in the last 6 months
• STEP I: Patients must not have uncontrolled intercurrent illness including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would limit compliance with the study, or a prior history of Stevens Johnson Syndrome
• STEP I: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 (PS 3 allowed if secondary to pain)
• STEP I: Patients with monoclonal gammopathy of undetermined significance or asymptomatic multiple myeloma are not eligible
• STEP I: Patients must not have grade 2 or higher peripheral neuropathy by Common Terminology Criteria for Adverse Events (CTCAE) 4.0
• STEP I: Patients must not have active, uncontrolled infection
• STEP I: Patients may have a history of current or previous deep vein thrombosis or pulmonary embolism but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation
• STEP I: Patients should not have New York Heart Association classification III or IV heart failure or myocardial infarction within the previous 6 months
• STEP I: Patients with a history of prior malignancy are eligible provided they were treated with curative intent and do not require active therapy (currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast are not excluded)
• STEP I: Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide 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 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
• STEP I: Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking lenalidomide and for 4 weeks after stopping treatment
• STEP I: The following patients will be excluded:
  • Pregnant women
  • Nursing women
• STEP I: Human immunodeficiency virus (HIV) infection is not excluded; known HIV positive patients must meet the following criteria:
  • Cluster of differentiation (CD(4 cell count >= 350/mm^3
  • No history of acquired immune deficiency syndrome (AIDS)-related illness
  • Not currently prescribed zidovudine or stavudine
• STEP I: Patient enrolling to this study must agree to register to the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
• STEP I: Patients must be willing to provide biological samples as required by the study
• STEP II: Patients must not have experienced progression on step 1 induction therapy
• STEP II: Step 2 registration must be within 28 days of completing step 1 therapy
• STEP II: Patients must not have received any non-protocol therapy outside of the assigned induction therapy
• STEP II: ECOG performance status 0, 1, or 2 (PS 3 allowed if secondary to pain)
• STEP II: Any adverse event related to step 1 therapy must have resolved to grade 2 or less
• STEP II: Hemoglobin >= 8 g/dL
• STEP II: Platelet count >= 75,000 cells/mm^3
• STEP II: Absolute neutrophil count >= 1000 cells/mm^3
• STEP II: Calculated creatinine clearance >= 30 mL/min
• STEP II: Bilirubin =< 1.5 mg/dL
• STEP II: SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of normal
• STEP II: FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide 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 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
• STEP II: Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse, while taking lenalidomide and for 4 weeks after stopping treatment
• STEP II: The following patients will be excluded:
  • Pregnant women
  • Nursing women
• STEP II: Patient enrolling to this study must agree to register to the mandatory RevAssist program and be willing and able to comply with the requirements of RevAssist