DISEASE CHARACTERISTICS:

• Histologically confirmed CD20+ multiple myeloma

  • CD20+ disease defined as co-expression of CD20 on ≥ 25% of the clonal plasma cell population as defined by immunohistochemical or flow cytometric staining of a bone marrow or plasmacytoma specimen obtained at study entry

    • For flow cytometry, this is determined by calculating the frequency of CD20+ CD138+ double-positive cells within the total CD138+ plasma cell population
    • For immunohistochemistry, this is determined by dual staining for CD20 and the involved clonal light chain (kappa or lambda), with a determination of the percent double-positive (≤ 25% or ≥ 25%)
• Symptomatic multiple myeloma that has relapsed or progressed after at least 1 prior anti-myeloma therapeutic regimen

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 16 weeks (4 months)
• ANC ≥ 1,500/μL (unless low ANC due to multiple myeloma)
• Platelets ≥ 100,000/μL (unless low platelets are due to multiple myeloma)
• Serum bilirubin ≤ 2.0 mg/dL
• AST, ALT, and alkaline phosphatase < 3 times upper limit of normal
• Serum creatinine ≤ 2.5 mg/dL
• Able to understand the investigational nature of lenalidomide and rituximab combination therapy and to give informed consent
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception at least 28 days before, during, and for at least 28 days after completion or discontinuation of study treatment
• Able to take acetylsalicylic acid (ASA) (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)
• Prior malignancies with a disease free interval of ≥ 5 years allowed
• No history of thromboembolic disease within the past 6 months, regardless of anticoagulation
• No myocardial infarction within the past 6 months
• No New York Hospital Association class III or IV heart failure
• No uncontrolled angina
• No severe uncontrolled ventricular arrhythmias
• No active hepatitis B or C infection
• No HIV 1or 2 positivity
• No acute ischemia or active conduction system abnormalities as evidenced by ECG
• No history of hypersensitivity reactions to lenalidomide, thalidomide, or rituximab
• No other medical condition or laboratory evaluation that, in the treating physician's or principal investigators' opinion, makes the patient unsuitable to participate in this clinical trial
• No concurrent active malignancy other than nonmelanoma skin cancers or carcinoma-in-situ of the cervix

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since prior therapy, including radiotherapy
• Prior lenalidomide or thalidomide allowed
• No prior rituximab