Inclusion Criteria

DISEASE CHARACTERISTICS:

- Symptomatic multiple myeloma

- Previously treated disease meeting one of the following criteria:

- Have light-chain amyloidosis that has been treated with at least one prior
regimen

- Symptomatic (relapsed or refractory) multiple myeloma

- Patients must have received 1-3 treatment regimens

- Induction therapy followed by autologous stem cell transplantation and
consolidation considered one regimen

- Measurable disease, as defined by 1 of the following:

- Serum monoclonal protein ≥ 1.0 g by protein electrophoresis

- More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis

- Serum immunoglobulin free light chain (FLC) > 10 mg/dL and an abnormal FLC ratio

- Measurable soft tissue plasmacytoma, not previously irradiated

- More than 30% plasma cells in bone marrow

- At least 10% plasma cells as measured by bone marrow aspirate, bone marrow biopsy, or
labeling index

- No monoclonal gammopathy of undetermined significance (not applicable for patients
with amyloid)

- No smoldering myeloma (not applicable for patients with amyloid)

PATIENT CHARACTERISTICS:

- ECOG performance status 0, 1, or 2

- ANC ≥ 1,000/μL

- Platelet count ≥ 75,000/μL

- Creatinine ≤ 2.5 mg/dL

- Not pregnant or nursing

- Women must refrain from breastfeeding during study participation and for at
least 28 days after discontinuation of study drug

- Negative pregnancy test

- Fertile female patients must use two reliable forms of contraception simultaneously
at least 28 days before beginning, during, and at least 28 days after completion of
study drug

- The two methods of reliable contraception must include one highly effective
method (i.e., intrauterine device [IUD], hormonal [birth control pills,
injections, or implants], tubal ligation, or partner's vasectomy) and one
additional effective (barrier) method (i.e., latex condom, diaphragm, or
cervical cap)

- Fertile male patients must use a latex condom (even if they have undergone a prior
vasectomy) while having intercourse with any woman, while taking the drug and for 28
days after stopping treatment

- Men must agree to abstain from donating semen or sperm during study participation and
for 28 days after discontinuation of study drug

- Willing to abstain from donating blood during study participation and for 28 days
after discontinuation of study drug

- No uncontrolled infection

- No other active malignancy

- No New York Heart Association class III or IV cardiac disease (all patients)

- Serum troponin T > 0.10 ng/mL (amyloid patients only)

- No known positivity for HIV or active hepatitis infection

- No active deep vein thrombosis or pulmonary embolism that has not been
therapeutically anticoagulated

- No condition, including the presence of laboratory abnormalities, that places the
patient at unacceptable risk for participating in the study or confounds the ability
to interpret data from the study

- No known hypersensitivity to thalidomide or lenalidomide including development of
erythema nodosum if characterized by a desquamating rash

- No peripheral neuropathy > grade 2

PRIOR CONCURRENT THERAPY:

- All previous cancer therapy, including chemotherapy and investigational agents, must
have been discontinued ≥ 2 weeks prior to study registration

- No radiotherapy ≤ 14 days prior to study registration

- No other concurrent anti-myeloma therapy

- No concurrent radiotherapy, except for palliation of a single painful bone lesion or
fracture

- Routine concurrent bisphosphonate therapy allowed for patients with myeloma bone
disease

- Willing and able to take aspirin or alternate prophylactic anticoagulation