Background 18-F fluorodeoxyglucose (FDG) uptake in the liver was used as a reference to characterize a complete molecular response (CMR) using positron emission tomography/computed tomography imaging (PET/CT) in patients undergoing treatment for newly diagnosed multiple myeloma, according to findings published in the Journal of Clinical Oncology.1
In order to determine response to treatment in the setting of multiple myeloma, the bone marrow (BM) needs to be assessed and the presence of any extramedullary disease (EMD) needs to detected. While FDG-PET/CT has become the preferred imaging method for the detection of minimal residual disease (MRD) in both of these compartments following treatment, and is considered complementary to the use of flow cytometry for identifying MRD in the bone marrow, standardized FDG-PET/CT criteria are needed to define CMR after therapy.
“To date, few indications to interpret FDG-PET/CT after therapy have been proposed or validated,” the study investigators noted.
This study relied on data from imaging substudies of 2 randomized, open-label, multicenter, phase 3 clinical trials of 228 transplant-eligible patients with newly diagnosed multiple myeloma treated with modern-era regimens in which at least 1 arm of each study also underwent autologous stem cell transplantation (ASCT).2,3
Whole-body PET/CT, including skull, upper limbs, and femurs, was performed at diagnosis, after induction therapy, and at completion of treatment but prior to maintenance therapy, if administered.
“In particular, BM metabolic state, focal lesions (FLs; number and metabolic state), and EMD (site, number, and metabolic state) were checked and reported. FDG uptake degree was visually quantiﬁed in the target lesion according to the 5-point Deauville scale (DS) adopted for PET scans in lymphomas (FL score [FS]) and in the BM out of FLs (BM score [BMS]),” the study authors clarified. Semiquantitative measures of FDG uptake by the liver and mediastinal blood pool were also determined.
The primary objectives of these imaging substudies were “to deﬁne criteria for PET CMR after therapy (PET MRD deﬁnition) by testing the prognostic impact of such criteria on [progression-free survival (PFS)].” A secondary objective was to assess whether these criteria were associated with overall survival (OS).
A key finding of this study was that, compared with a FS and a BMS of 4 or higher, a FS and a BMS less than 4, which was lower than the DS score for the liver, were independently associated with prolonged PFS on multivariate analysis (FS: hazard ratio [HR], 0.60; 95% CI, 0.37-0.95; P =.030; BMS: HR, 0.50; 95% CI, 0.26-0.97; P =.041).
In addition, on multivariate analysis, FS and BMS less than 4 were also independent predictors of prolonged OS (FS: HR, 0.34; 95% CI, 0.16-0.70; P =.004; BMS: HR, 0.25; 95% CI, 0.10-0.66; P =.005).
“On the basis of these results, we believe that reduction of FL and BM uptake lower than the liver (DS score below 4) can be proposed as the standardized deﬁnition of PET CMR after therapy within new PET response criteria,” the study investigators stated.
Nevertheless, they cautioned that prospective clinical trials are needed to validate these results, and to evaluate whether there is concordance between CMR as determined by FDG-PET/CT and MRD in the bone marrow by flow cytometry.
- Zamagni E, Nanni C, Dozza L, et al. Standardization of 18 F-FDG-PET/CT according to Deauville Criteria for metabolic complete response definition in newly diagnosed multiple myeloma. J Clin Oncol. Published online November 5, 2020. doi:10.1200/JCO.20.00386
- Attal M, Lauwers-Cances V, Hulin C, et al: Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376:1311-1320. doi:10.1056/NEJMoa1611750
- Cavo M, Gay F, Beksac M, et al: Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomiblenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): A multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020;7:E456-E468. doi:10.1016/S2352-3026(20)30099-5