In this study, Zamagni and colleagues from Bologna evaluated 192 patients with newly diagnosed myeloma using positron emission tomography integrated with computerized tomography (PET/CT) at the time of diagnosis, as well as after bortezomib-dexamethasone induction therapy followed by tandem high-dose melphalan and autologous stem cell transplantation. At the time of diagnosis, the finding of three or more focal lesions, standardized uptake value (SUV) > 4.2 for any lesion, and extramedullary disease (EMD) (defined as FDG-avid soft tissue not continuous with bone) portended shorter progression-free survival (PFS), whereas both SUV > 4.2 and EMD were associated with shorter overall survival (OS). Moreover, SUV > 4.2 persisting after bortezomib-dexamethasone induction therapy predicted shorter PFS. Most importantly, patients with negative PET/CT at three months post-transplant had significantly longer PFS and OS compared to patients whose scans remained positive. Finally, both identification of EMD and a lesion associated with SUV > 4.2 at baseline were found in multivariate analysis to be independent, adverse prognostic factors for PFS.
This is a landmark study. Multiple staging systems based upon clinical factors, laboratory features, and cytogenetics have been used over time to assess burden of disease and predict response to therapy in myeloma. Staging systems have evolved from the Durie-Salmon system of the past to the International Staging System of the present. Cytogentic analyses have defined standard and high-risk patient subgroups. Theses analyses have been used to stratify patients in innovative clinical studies that have identified treatment strategies that overcome some (t4;14 translocation), but not all (17p deletion), features predictive of adverse outcome to conventional treatments. More recently, genomic signatures have been correlated with response and outcome to conventional and novel therapies. Progress in assessment of bone disease in myeloma has paralleled progress in staging with bone surveys being superceded by magnetic resonance imaging and PET/CT scanning. In past studies, PET/CT scanning has been useful for both staging and prognosis in myeloma, particularly for the diagnosis of osseous and extraosseous plasmacytomas, with the caveat of high sensitivity and low specificity and the need to avoid dexamethasone therapy proximate to the study. PET/CT is particularly useful in myeloma because bone lesions will remain anatomically abnormal on plain films or magnetic resonance imaging even in the setting of response, whereas PET/CT can determine if anatomically abnormal sites have residual active disease. For example, Barlogie and colleagues have pioneered the use of PET/CT and biopsy of positive lesions to define more stringently complete response (CR) on the one hand, and to alter treatment strategy in the setting of persistent positivity and residual active disease on the other.1
In Brief
Zamagni and coworkers provide additional support for the prognostic utility of PET/CT. Importantly, they establish its prognostic utility at time of diagnosis and then show, in uniformly treated patients, that persisent positivity after induction and at three months post-transplant adversely affects outcome. Especially in this era of evolving novel therapies, in which both the extent and frequency of response is greater, the capacity of PET/CT to provide an additional independent factor that can be used to define prognosis and detect residual disease is particularly noteworthy. For staging at time of diagnosis or relapse, including detection of EMD, PET/CT is very sensitive and has the advantage of detecting active disease. Comparison of PET/CT with other imaging modalities, such as magnetic resonance imaging, may provide additional diagnostic and prognostic information. In terms of detecting minimal residual disease after induction, transplantation, or even maintenance therapy, the utility of PET/CT should be compared with multicolor flow cytometry and allele-specific polymerase chain reaction (PCR) methods. The International Myeloma Working Group (IMWG) criteria for stringent CR already includes absence of residual bone marrow disease by multicolor flow cytometry, whereas IMWG molecular CR demands that the allele-specific PCR be negative. Following comparative studies, PET/CT may be incorporated into these CR criteria, resulting in even more accurate response assessment and better informed decisions regarding the need for further therapy.
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Competing Interests
Dr. Anderson indicated no relevant conflicts of interest.
