Evaluation of the Impact of the Update SMM Criteria on the Natural History of SMM to Establish New Recommendations.

Inclusion Criteria:

• Age ≥ 18 years.
• SMM defined by IMWG 2014 criteria

1. Serum monoclonal protein (IgG or IgA) ≥30 g/L and/or urinary monoclonal protein ≥500 mg per 24 h and/or clonal bone marrow plasma cells 10-60%
2. Absence of myeloma defining events or amyloidosis

• Diagnosed less than 1 year before the inclusion
• Able and willing to give valid written informed consent. Patients must give writteninformed consent (IC) in accordance with institutional and local guidelines.

Exclusion Criteria:

• Previous antimyeloma treatment including bisphosphonates
• Second Primary Malignancy and/or auto-immune disease treated by immunosuppressivedrugs.
• Evidence of end organ damage that can be attributed to the underlying SMM:

1. Hypercalcaemia: serum calcium >0.25 mmol/L (>10 mg/L) higher than the upper limitof normal or >2.75 mmol/L (>110 mg/L)
2. Renal insufficiency: creatinine clearance <40 mL/min or serum creatinine >177 μmol/L (>20 mg/L)
3. Anaemia: haemoglobin value of >2 g/dL below the lower limit of normal, or ahaemoglobin value <10 g/dL
4. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, orPositron Emission Tomography-Computed Tomography (PET-CT)

• Presence of one of the following biomarkers of malignancy:

1. Clonal bone marrow plasmocytosis ≥60%
2. Involved/uninvolved serum Free Light Chain (FLC) ratio ≥ 100 (The involved freelight chain must be ≥100 mg/L)
3. Presence of one or more focal lesions on MRI studies (each focal lesion must be 5mm or more in size)

• History of malignancy other than SMM within 3 years before inclusion
• Amyloidosis
• POEMS syndrome
• Contraindication to MRI
• Pregnancy
• Nursing mother
• Legally protected adults (under judicial protection, guardianship, or supervision)