In this paper, Bartel et al., from Barlogie’s group at the University of Arkansas for Medical Sciences, compared the utility of F18-fluorodeoxyglucose positron emission tomographic (FDG-PET) imaging to skeletal x-ray survey and magnetic resonance imaging in multiple myeloma (MM). In the context of their Total Therapy (TT)-3 program, FDG-PET was the leading independent factor predictive of decreased event-free and overall survival. Importantly, suppression of FDG uptake after induction therapy predicted for a superior outcome after transplantation. This study demonstrates the potential utility of FDG imaging for staging and assessing response to therapy in MM.
Bone disease detected by skeletal survey occurs in 80 percent of patients with MM and is the major factor limiting performance status and quality of life. Magnetic resonance imaging is more sensitive, since it can detect marrow infiltration even before bone destruction. However, a very sensitive technique to assess sites of MM activity, localized or diffuse within the bone marrow, is needed both for staging at diagnosis and for assessing response to therapy. Those patients with nonsecretory MM or extramedullary MM are important MM subgroups, in whom such technologies are necessary for optimal treatment. FDG-PET scanning represents such a technology, with FDG uptake correlating with biology and disease activity, and concomitant PET detecting anatomic abnormalities. Importantly, suppression of FDG activity has shown prognostic value in studies in lymphomas and solid tumors, and FDG scanning has been approved for reimbursement by CMS. To date, however, there have not been studies examining the role of FDG-PET scanning in staging or prognosis of uniformly treated MM patient populations.
The authors of this study have been pioneers in evaluating TT treatment programs — double autologous transplant protocols — which have sequentially evolved to incorporate thalidomide (TT2) and novel therapies bortezomib and lenalidomide (TT3). In the TT3 studies, sustained complete remissions, even in patients with cytogenetic abnormalities, are now being observed. In other studies, the combination of bortezomib, lenalidomide, and dexamethasone used as initial therapy has been shown to achieve 100 percent response rates, with 71 percent very good partial response or better. These high response rates measured with standard International Myeloma Working Group criteria have identified the need for more sensitive techniques to evaluate both extent of disease at diagnosis and response to treatment. In this study, the authors showed that the number of focal lesions on PET, the presence of extramedullary disease, and the number of osteolytic lesions adversely impacted event-free and overall survival. More than three focal lesions on PET conferred adverse prognosis even in the lowrisk subgroup defined by gene array, whereas patients with high-risk MM, defined by gene array, uniformly did poorly. Most importantly, the complete suppression of FDG activity prior to first transplantation conferred superior outcome in both low- and high-risk gene-array-defined subgroups; conversely, the lack of suppression was associated withpoor outcome and indicates the need for alternative strategies.
These studies have important clinical applications in MM since they suggest that FDG-PET scanning is useful both for staging and assessing response to therapy and may, therefore, allow for individualized treatment strategies. Further prospective trials of FDG-PET scanning in uniformly treated MM patients, particularly in the context of novel treatment paradigms achieving high extent and frequency of response, are needed to confirm its value and ultimately incorporate its use in guidelines for disease diagnosis, staging, and assessing response to therapy in MM.
Dr. Anderson receives research funding and/or consultancy fees from Millennium, Celgene, and Novartis.