Advanced Skeletal Imaging Redefines the Management of Plasma Cell Disorders

In this issue of Journal of Clinical Oncology, Dimopoulos and thought leaders in the field of myeloma, representing the International Myeloma Working Group, provide evidence-based, consensus recommendations on the use of magnetic resonance imaging (MRI) in a number of plasma cell disorders. Their recommendations are practice changing. When new techniques are introduced for patient evaluation, they often add expense for patients but do not affect management. These recommendations affect therapeutic decision making for patients with plasma cell disorders and represent an update of earlier International Myeloma Working Group recommendations. The paper focuses on the use of MRI. However, data on the use of positron emission tomography (PET) combined with computed tomography (CT) is also applicable to decision making in patients with plasma cell disorders. This consensus publication focuses on whole-body MRI. The recommended substitution of MRI of the axial skeleton for when whole-body MRI is not available results in a failure to recognize almost 50% of skeletal lesions in myeloma. The use of PET/CT, which provides a full-body scan, becomes an alternative for many. The sensitivity and specificity of FDG PET for detecting lesions in myeloma is 96%, and the specificity is 77%; it is particularly useful for the assessment of extramedullary disease. In a meta-analysis of 18 studies comprising 800 patients with myeloma, FDG PET detected osteolytic lesions with a sensitivity of 80% to 90% and a specificity of 80% to 100%. A higher number of lesions were revealed with PET/CT than with MRI. Unlike MRI, however, PET/CT is not sensitive to diffuse bone marrow infiltration, which is well detected by MRI. PET/CT can distinguish old from new fractures based on uptake. MRI should, however, be preferred when the vertebral bodies are suspected to be involved and the risk of vertebral fracture is to be assessed. No conclusions can be drawn on the superiority of one technique over the other in the imaging of patients with plasma cell disorders, but it appears both have a role. A comparison of the sensitivity of wholebody MRI versus traditional skeletal radiography was conducted in 171 patients with plasma cell dyscrasias. In the group of patients who were evaluated by whole-body CT, 23% had lesions that were not detected with plain radiography. In the second group, whole-body MRI revealed lesions in 16% of patients that were not detected by skeletal radiographs. All lesions detected by skeletal radiography were also detected by whole-body MRI and whole-body CT, each was superior to standard radiography. Patients with multiple myeloma who lack symptoms should not be treated. This group of smoldering multiple myeloma patients, lacking the cardinal features of anemia as a result of marrow infiltration, hypercalcemia related to osteolysis, renal impairment due to cast nephropathy, or compression fractures and lytic lesions, should be observed. Recent questions have been raised regarding the wisdom of this recommendation. There is tension around not wishing to treat patients with chemotherapy if they are not destined to develop active disease for many years. However, there is a subset of patients in whom the withholding of therapy puts them at greater risk of morbidity than early intervention. If the risk of active overt multiple myeloma is 70% at 2 years, then these patients actually have multiple myeloma and should be treated. This entity has been referred to as high-risk smoldering multiple myeloma, and a survival benefit has been demonstrated with the use of lenalidomide with or without dexamethasone. The difficulty is defining what constitutes high-risk multiple myeloma. Half of patients with smoldering multiple myeloma remain progression free at 5 years. However, risk factors that predict rapid development of overt disease have been identified. High-risk disease exists if an aberrant immunophenotype of plasma cells exceeds 95%. Unfortunately, this diagnostic study is not widely available. Others have proposed bone marrow that contains more than 60% plasma cells, high levels of circulating plasma cells, a ratio of involved to uninvolved free light chains exceeding 100, high-risk genetics, or heavy light chain pair suppression; however, there is no general agreement on which criteria should be adopted. Advanced skeletal imaging can identify patients with asymptomatic myeloma having focal bone lesions that would justify therapy. In a study of 149 patients with asymptomatic myeloma, focal bone lesions were found in 28%, and the presence of focal bone lesions were predictive of progression into symptomatic myeloma. A diffuse infiltration pattern on MRI also was predictive for progression, suggesting that whole-body MRI could reclassify asymptomatic patients into those who would benefit from early therapy. Serial whole-body MRI in smoldering myeloma can identify new focal lesions, an increase in the diameter of existing focal lesions, or progression of diffuse marrow infiltration as a predictor of progression and is seen in 49% of patients. Patients with a stable MRI did not have a higher risk of progression, even when small focal lesions were present. In patients with asymptomatic myeloma, MRI or FDG PET should be performed to ensure that these patients would not benefit from early intervention. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 6 FEBRUARY 2