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lesion at the initial work-up is associated with a higher risk of progression to full-blown MM. The current revised IMWG criteria propose that the presence of at least two focal MRI lesions defines symptomatic MM.19

Additionally, MRI is

This is of utmost importance, because follow-up and treatment of patients with SMM at high-risk of progression into MM has gained importance over the past years.22

suitable for follow-up of patients with MM and SMM. In symptomatic disease, longitudinally performed MRIs before and after high-dose therapy revealed that the presence of focal lesions after therapy is associated with adverse outcome, whereas the disappearance translates into prolonged overall survival.20 Furthermore, a recent study in SMM demonstrated that a progressive focal or diffuse bone marrow infiltration in longitudinally performed MRIs predicts the occurrence of CRAB criteria and therefore the transition to symptomatic disease.21

therapy according to current guidelines28 should be applied if necessary. Also, a whole-body MRI should be performed to identify focal or diffuse marrow infiltration. This does not only contribute to risk assessment in MGUS17

but might

also help to discriminate benign from malignant osteoporosis. Because signal intensity in MRI correlates with plasma cell infiltration,29

whole-body MRI

provides a surrogate for disease activity throughout the whole bone marrow. This is superior to bone marrow biopsies, which are performed in a small anatomical region. In our opinion, imaging studies should only be repeated in MGUS if there is evidence for progressive disease from the clinical follow-up. Such clinical follow-up should be performed every 6–12 months and should include assessment of new bone pain as well as blood tests for haemoglobin, serum creatinine levels and urine/serum monoclonal protein.30


advantages of MRI compared with other imaging modalities include the excellent assessment of patients with extramedullary MM or plasmocytoma and the superiority compared with CT when it comes to the detection of spinal cord injury. Gadolinium-based contrast agents can be applied safely to increase sensitivity of T1-weighted sequences23

be implemented in dynamic contrast- enhanced studies (DCE-MRI) to assess bone marrow microcirculation.24


In general, recommendations for initial imaging in SMM is the same as in MGUS and include a whole-body CT and MRI for staging and risk assessment. Based on our recent data that demonstrated prognostic significance of longitudinally performed

and Another

promising method that can be realised on most clinical scanning devices is diffusion-weighted imaging (DWI), that provides surrogate markers for bone marrow cellularity and microperfusion without the need for applying any contrast agent.25,26

Major downsides of

MRI are its limited availability, high costs and relatively long examinations compared with CT, although modern scanners can acquire whole-body MRIs in less than 45 minutes.

Imaging specific stages of disease MGUS

Based on IMWG recommendations, we currently recommend performing a low-dose whole-body CT at primary diagnosis of MGUS to rule out osteolytic bone lesions.3

Because patients with

MGUS are at higher risk of developing osteoporosis and osteoporosis related- fractures,27

we furthermore endorse 14

quantification of bone mineral density at the primary work-up. Osteoprotective

disease. In symptomatic MM, the radiological extend of intra- and extramedullary involvement needs to be assessed before the start of systemic therapy, because some patients, for example, those with pathological fractures or painful osteolyses, are candidates for local radiation therapy or orthopaedic surgery. CT and MRI should be repeated after the end of primary therapy to identify residual disease and reassess stability, especially of the vertebral column. Recent studies showed that patients are at risk for vertebral compression fractures, even if remission is achieved upon therapy.32


of bony structures after successful therapy usually takes months. During that time, patients exhibit a higher risk for fractures. In that context, CT and MRI to identify vital MM cells in

corresponding osteolyses might prevent misinterpretation of novel fractures as progression of disease. Further imaging should only be performed when clinically indicated, for example, if the patients has new symptoms (bone pain, neurological symptoms) or serological evaluation (usually performed every three months) shows progressive disease. The occurrence of any CRAB criteria during follow-up should also automatically

"Magnetic resonance imaging enables the assessment of bone marrow infiltration before bone destruction has occurred"

whole-body MRIs in patients with SMM,21 we recommend annual whole-body MRIs for follow-up in the first five years from primary diagnosis. If there is evidence for progressive disease from clinical follow- up, or whole-body MRI, a CT should be performed to rule out the occurrence of osteolytic lesions. We chose a five-year period for annual whole-body MRIs because the risk of progression from SMM into MM is 10% per year during the first five years from diagnosis.31

After the

first five years, the risk of progression drops to 1% per year and is the same as for MGUS patients.31

If a patient has not

progressed into symptomatic MM during the first five years and has no signs of disease progression, an MGUS-like cause of disease is more likely.

Symptomatic MM

All patients should receive initial whole-body CT and MRI in symptomatic

trigger whole-body CT to rule out new osteolyses. In addition to the mentioned procedure in symptomatic MM, we recommend performing whole-body MRI every six months in patients with non-secretory or extramedullary MM, as serological evaluation remains challenging in this group of patients. l

References 1. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 2009;23(1):3–9.

2. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36(3):842–54.

3. Dimopoulos M et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of

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