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PET/CT imaging to determine remission in multiple myeloma patients

Thursday, October 15, 2015

Imaging studies with the radionuclide 18F labeled with fluorodeoxyglucose (18F-FDG) can be used to predict outcomes and refine the definition of complete response (CR) in patients with multiple myeloma (MM), according to investigators at the University of Bologna, in Italy. Clinical Oncology News invited Tomer M. Mark, M.D., MSc, associate professor of clinical medicine and associate director of the Myeloma Center to comment on the research. Read the whole article here. 

Tomer Mark, M.D.Tomer Mark, M.D. The role of PET/CT imaging in MM has been murky for some time. There is no dispute that the standard of practice skeletal survey in MM is highly insensitive. More than 30% of the cortical bone needs to be eroded before a lytic lesion can be detected by x-ray; thus, there is the potential to miss early disease (Clin Radiol 1967;18[2]:158-162, PMID: 6023348). A skeletal survey also lacks the power to detect extramedullary disease, which is a highly deleterious risk factor in myeloma. Several research groups have found PET/CT to detect MM activity, showing that increased number and FDG avidity of myelomatous lesions correlated with worse clinical outcomes.
In the report by Zamangi et al, we can see with their longitudinal data that patients who have a PET-positive lesion with high SUV at any point in their treatment course have a markedly decreased PFS and OS. Also of note was that a remarkably high number of patients (5% in this study) presented with what would have otherwise been silent extramedullary disease, thus elevating their risk for early progression and death dramatically.
In addition to defining baseline risk and early relapse, the other way that this can inform clinical decisions is by identifying patients in complete remission with residual disease activity. With the advent of available highly active novel agents in MM, patients are now regularly achieving deep responses. It is still evident, unfortunately, that the vast majority of patients who achieve complete remission in MM ultimately relapse. This outcome prompts an intensive effort to better define the level of minimal residual disease in patients who achieve immunofixation-negative status. PET/CT may provide a noninvasive way to detect residual disease activity and outline a high-risk group of patients otherwise in CR for intervention trials.
No guidelines exist delineating the optimal way to use PET/CT in MM. The repetition of a PET/CT scan yearly may present an undue radiation risk and certainly is more costly than skeletal survey. Other techniques that may mitigate the radiation dose needed, such as low-dose whole-body CT, are emerging (Clin Cancer Res 2014;20[23]:5888-5897, PMID: 25294899). PET/CT scans also can be associated with a high false-positive rate, which may lead to unnecessary interventions. Lastly, it is not yet known whether early intervention in incipient myeloma relapse would achieve better outcomes or simply be subject to lead-time bias.
However, Zamangi et al convincingly show that combining PET/CT with clinical and laboratory data represents one of the best available methods to monitor disease activity and baseline risk in MM. Their work likely will evolve into both a new staging system incorporating advanced radiologic imaging techniques with baseline cytogenetic and laboratory abnormalities to provide the most granular prognostic information available to help guide therapy for our patients.