Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

Inclusion Criteria:

• Diagnosis of smoldering multiple myeloma (MM) meeting the following criteria:

  • Asymptomatic high-risk disease
  • Bone marrow plasmacytosis with ≥ 10% plasma cells or sheet of plasma cells by bone marrow aspiration and/or biopsy
  • Abnormal serum free-light chain (FLC) ratio (< 0.125 or > 8.0) by serum FLC assay
  • No baseline bone lesions or plasmacytomas
  • No monoclonal gammopathy of undetermined significance
  • No immediate need for chemotherapy
• Measurable monoclonal protein in the serum ≥ 1.0 g/dL or urine ≥ 200 mg/24 hrs
• No lytic lesions on skeletal surveys and no hypercalcemia (i.e., ≥ 11 mg/dL)
• ECOG performance status 0-2
• ANC > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 11 g/dL
• Creatinine clearance > 30 mL/min
• Bilirubin < 1.5 mg/dL
• ALT and AST < 2.5 times upper limit of normal
• More than 6 months since active, uncontrolled seizure disorder
• Willing to take some form of anti-coagulation as prophylaxis if there is a history of or concurrent deep vein thrombosis or pulmonary embolism
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective methods of contraception for ≥ 28 days before, during, and ≥ 28 days after completion of study therapy
• Prior malignancy allowed provided treatment of curative intent was delivered and disease-free for time period considered appropriate for the specific cancer

• HIV-positive patients allowed provided the following criteria are met:

  • CD4 cell count ≥ 350/mm³
  • No history of AIDS-related illness

• No uncontrolled intercurrent illness including any of the following:

  • Uncontrolled hypertension
  • Symptomatic congestive heart failure
  • Unstable angina
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled psychiatric illness or social situation that would limit compliance with the study
  • Prior Stevens Johnson Syndrome
• No peripheral neuropathy ≥ grade 2
• No active uncontrolled infection
• No NYHA class III or IV heart failure
• No prior or concurrent systemic therapy or radiotherapy for MM
• No prior or concurrent erythropoietin

• No prior glucocorticosteroid for MM

  • Prior systemic glucocorticosteroid for non-malignant disorders allowed (prednisone equivalent ≤ 10 mg/day)
  • Prior or concurrent topical or localized glucocorticosteroid to treat non-malignant comorbid disorders allowed

• No concurrent bisphosphonates

  • Prior bisphosphonates or once-a-year intravenous bisphosphonate for osteoporosis allowed
• No concurrent zidovudine or stavudine for HIV-positive patients
• No concurrent chemotherapy including cyclophosphamide and stem cell mobilization