Inclusion Criteria:

- Diagnosed with previously treated multiple myeloma.

- Measurable disease assessed by one of the following ≤21 days prior to registration:

- Serum monoclonal protein ≥1 g by protein electrophoresis

- Urine monoclonal protein >200 mg on 24 hour electrophoresis

- Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio

- Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)

- NOTE: If both serum and urine m-components are present, both must be followed in
order to evaluate response.

- All previous cancer therapy including chemotherapy, radiation, hormonal therapy and
surgery, must be discontinued ≥2 weeks prior to registration.

- Age ≥18 years.

- ECOG performance status 0-2.

- Acceptable organ and marrow function ≤21 days prior to registration:

- ANC ≥1000/mm³

- Platelet count ≥75,000/mm³

- Total bilirubin ≤2 mg/dL

- AST and ALT ≤3 x upper limit of normal

- Renal impairment at baseline as measured by serum creatinine clearance (CrCl) ≤60
mL/min ≤21 days prior to registration.

- Females of Childbearing Potential (FCBP) must have a negative pregnancy test within
10-14 days and again within 24 hours of starting Cycle 1 and must use an effective
double-method contraception for ≥28 days prior to, during, and for ≥28 days after
completion of study therapy.

- Able to take required prophylactic anticoagulation.

- Able to understand and willingness to sign a written informed consent.

- Willing to provide blood samples for research purposes (Mayo Clinic sites only).

- If previously received lenalidomide, demonstration of clinical response of any
duration or stable disease with progression-free interval of ≥6 months from start of
that therapy.

Exclusion Criteria:

- Concurrent use of other anti-cancer agents or treatments. NOTE: Growth factors and
bisphosphonates are allowed as medically indicated. Steroids may be used with an
equivalency of up to 20 mg of Prednisone per day as long as the dose has not been
adjusted upwards in past 2 weeks prior to study registration.

- Uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection requiring IV antibiotics

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Uncontrolled cardiac arrhythmia

- Psychiatric illness/social situation that would limit compliance with study
requirements.

- Any of the following as this regimen may be harmful to a developing fetus or nursing
child:

- Pregnant women

- Breast-feeding women

- Men or women of childbearing potential or their sexual partners who are
unwilling to employ adequate contraception.

- HIV-positive patients on combination antiretroviral therapy.

- Known hypersensitivity to thalidomide or other immunomodulatory drugs.

- History of Stevens-Johnson syndrome characterized by a desquamating rash while taking
thalidomide or similar drugs.

- Other active malignancy except for non melanoma skin cancer or in situ cervical or
breast cancer.

- Concurrent radiation therapy, except for palliation of a single painful bone lesion
or fracture.