Inclusion Criteria

- INCLUSION CRITERIA:

Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma
confirmed by the Laboratory of Pathology, NCI based on the International Myeloma Working
Group Criteria:

- Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells
greater than or equal 10 %

- Absence of anemia: Hemoglobin > 10 g/dl

- Absence of renal failure: serum creatinine < 2.0 mg/dL Absence of hypercalcemia: Ca
< 10.5 mg/dl

- Absence of lytic bone lesion

Measurable disease within the past 4 weeks defined by any one of the following:

- Serum monoclonal protein greater than or equal to 1.0 g/dl

- Urine monoclonal protein > 200 mg/24 hour

- Serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratio

Age greater than or equal to 18 years. Because no dosing or adverse event data are
currently available on the use of carfilzomib in combination with lenalidomide in patients
< 18 years of age, children are excluded from this study, but may be eligible for future
pediatric trials.

ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).

Patients must have normal organ and marrow function as defined below:

- absolute neutrophil count greater than or equal to1.0 K/uL

- platelets greater than or equal to75 K/uL

- hemoglobin greater than or equal to 8 g/dL(transfusions are permissible)

- total bilirubin less than or equal to 1.5 times institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) less than or equal to 3.0 times institutional upper limit of
normal

- Creatinine Clearance greater than or equal to 60 ml/min. CrCl will be calculated by
Cockcroft Gault method. CrCl (calculated) = (140 - Age) times Mass (in kilograms)
times [0.85 if Female] 72 times Serum Creatinine (in mg/dL). If calculated CrCl based
on Cockcroft-Gault method is < 60 mL/min, patient will have a 24 hr urine collection
to measure CrCl. The measured CrCl must also be greater than or equal to 60 ml/min.

High-risk SMM per Mayo Clinic or Spanish PETHEMA criteria

All study participants must be registered into the mandatory RevAssist program, and be
willing and able to comply with the requirements of RevAssist.

The effects of carfilzomib and lenalidomide on the developing human fetus are unknown. For
this reason and because immunomodulatory agents as well as other therapeutic agents used
in this trial are known to be teratogenic, women of childbearing potential and men must
agree to use adequate contraception. Females of childbearing potential (FCBP) must have a
negative serum or urine pregnancy test within 10 - 14 days and again within 24 hours prior
to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and
must either commit to continued abstinence from heterosexual intercourse or begin TWO
acceptable methods of birth control, one highly effective method and one additional
effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide.
FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom
during sexual contact with a FCBP even if they have had a successful vasectomy. All
patients must be counseled at a minimum of every 28 days about pregnancy precautions and
risks of fetal exposure. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately.

Ability of subject to understand and the willingness to sign a written informed consent
document.

EXCLUSION CRITERIA:

Patients who are receiving any other investigational agents.

Concurrent systemic treatment or prior therapy within 4 weeks for SMM

- Treatment with corticosteroids for other indications is permitted

- Patients with prior proteasome inhibitor therapy will be excluded

Patients with a diagnosis of MM

Contraindication to any concomitant medication, including antivirals, anticoagulation
prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy

History of allergic reactions attributed to compounds of similar chemical or biologic
composition to carfilzomib or lenalidomide agents used in study, such as bortezomib or
thalidomide.

Uncontrolled hypertension or diabetes

Pregnant or lactating females. Pregnant women are excluded from this study because
Carfilzomib/Lenalidomide are agents with the potential for teratogenic or abortifacient
effects. Because there is an unknown but potential risk for adverse events in nursing
infants secondary to treatment of the mother with Carfilzomib/Lenalidomide, breastfeeding
should be discontinued if the mother is treated with Carfilzomib/Lenalidomide. These
potential risks may also apply to other agents used in this study

Significant cardiovascular disease with NYHA Class III or IV symptoms, or hypertrophic
cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior
to enrollment, or unstable angina, or unstable arrhythmia

Active hepatitis B or C infection

Has refractory GI disease with refractory nausea/vomiting, inflammatory bowel disease, or
bowel resection that would prevent absorption

Significant neuropathy > Grade 2 at the time of first dose or within 14 days of enrollment

Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations within 2 weeks that would limit
compliance with study requirements.

History of other malignancy (apart from basal cell carcinoma of the skin, or in situ
cervix carcinoma) except if the patient has been free of symptoms and without active
therapy during at least 5years

Major surgery within 1 month prior to enrollment