Inclusion criteria

          -  Patients must have histologically or cytologically confirmed Smoldering Multiple
             Myeloma based on the 2014 International Myeloma Working Group Criteria(20):

          -  Serum M-protein ≥3.0 g/dl, or urinary monoclonal protein >500 mg per 24 hours, and/or
             monoclonal bone marrow plasma cells ≥10-60 %

          -  Absence of CRAB symptoms:

          -  anemia: Hemoglobin <6.2 mmol/L (10 g/dl) or a hemoglobin value of >1.2 mmol/L (2 g/dL)
             below the lower limit of normal

          -  renal failure: serum creatinine > 2.0 mg/dL or creatinine clearance < 40 ml/min

          -  hypercalcemia: serum calcium >0·25 mmol/L (>1 mg/dL) higher than the upper limit of
             normal or >2·75 mmol/L (>11 mg/dL)

          -  Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT

          -  Absence of myeloma defining events:

          -  Involved/uninvolved serum free light chain ratio ≥100 with involved free light-chain
             concentration ≥10 mg/dl

          -  Presence of 2 or more focal lesions by MRI (2 of which at least 5 mm)

          -  Clonal bone marrow plasma cell percentage ≥60%

          -  Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic
             and/or the PETHEMA criteria:

          -  3 factors of Mayo Clinic criteria:

          -  Bone marrow plasma cells ≥10 %

          -  Serum M-protein ≥ 3 g/dl

          -  Serum free light-chain ratio <0.125 or >8

          -  And/or 2 factors of PETHEMA criteria:

          -  Of the plasma cell population ≥95% abnormal plasma cells (presence or absence of CD38,
             CD56, CD19 and/or CD45)

          -  Immunoparesis, a reduction (below the lower normal limit) in the levels of 1 or 2 of
             the uninvolved immunoglobulins (Ig)

          -  Measurable disease defined by any one of the following:

          -  Serum monoclonal protein ≥ 1.0 g/dl

          -  Urine monoclonal protein >200 mg/24 hour

          -  Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio
             (reference 0.26-1.65)

          -  Age >18 years

          -  WHO/ECOG performance status <2 (see Appendix C).

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

          -  Absolute neutrophil count >1.0 x109 /L

          -  Platelets ≥75 ×109 /L

          -  Hemoglobin ≥10 g/dL (>6.2 mmol/l)

          -  Total bilirubin <1.5 x institutional upper limit of normal

          -  AST(SGOT)/ALT(SGPT) ≤3.0 × institutional upper limit of normal

          -  Creatinine Clearance ≥ 50 ml/min. CrCl will be calculated by Cockcroft-Gault method or
             eGFR (Modified Diet in Renal Disease [MDRD])

          -  Females of childbearing potential must have a negative serum or urine pregnancy test
             within 10 - 14 days prior to entry and again within 24 hours of starting lenalidomide
             treatment; (see 9.1.4)

          -  Patients must be willing and capable to use adequate contraception during and after
             the therapy (all men, all pre-menopausal women) (see 9.1.4.); Patients must be able to
             adhere to the requirements of the Lenalidomide Clinical Trial Pregnancy Prevention
             Plan;

          -  Written informed consent

          -  Patient is capable of giving informed consent

        Exclusion criteria

          -  Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)

          -  Amyloid Light-chain (AL) amyloidosis

          -  Patients who are receiving any other investigational agents.

          -  Concurrent systemic treatment or prior therapy within 4 weeks for SMM (if a patient
             has received any previous SMM therapy this must be discussed with the Principal
             Investigator before inclusion in the trial).

        Treatment with corticosteroids for other indications is permitted

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

          -  History of allergic reactions attributed to immunomodulatory agents and proteasome
             inhibitors.

          -  Uncontrolled hypertension or diabetes

          -  Pregnant or lactating females.

          -  Significant cardiovascular disease with NYHA grade 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

          -  Known or suspected HIV infection

          -  Incidence of gastrointestinal disease that would prevent absorption.

          -  Significant neuropathy ≥Grade 3 or grade 2 with pain within 14 days of enrollment

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection.

          -  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 5 years

          -  Major surgery within 1 month prior to enrollment

          -  Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures
             as described at paragraph 9.1.4

          -  Any psychological, familial, sociological and geographical condition potentially
             hampering compliance with the study protocol and follow-up schedule.