Inclusion Criteria

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