SAN DIEGO – Having less than three focal lesions on FDG-PET/CT (fluorodeoxyglucose positron emission tomography integrated with computed tomography) when beginning lenalidomide maintenance therapy predicted significantly higher rates of progression-free and overall survival among patients with newly diagnosed multiple myeloma.
Survival in this prospective study of 102 patients also correlated with FDG uptake that did not exceed the level of the liver (Deauville score less than 3), reported Elena Zamagni, MD, PhD, of Bologna (Italy) University. The findings highlight FDG-PET/CT as “a powerful prognostic marker for survival, both in terms of number and score of focal lesions,” she said during an oral presentation at the annual meeting of the American Society of Hematology.
Although FDG-PET/CT is “well recognized” for staging and evaluating prognosis in multiple myeloma, a “major inconsistency in methodology between studies” inspired the current analysis, Dr. Zamagni said. “Different groups have used different interpretation criteria and arbitrary cutoffs with very variable results, especially in terms of posttreatment and borderline cases,” she noted.
Therefore, researchers from eight participating centers evaluated FDG-PET/CT scans from 103 patients with newly diagnosed multiple myeloma who were part of the randomized phase III EMN02 trial. Scans were performed at diagnosis, at the start of induction therapy, and just before patients started maintenance therapy with lenalidomide. Five nuclear medicine experts reviewed the scans in a blinded manner.
About 34% of patients had positive focal lesions on FDG-PET/CT at the start of maintenance, Dr. Zamagni said. After a median follow-up of 2 years, rates of progression-free survival were 84% in those with fewer than three focal lesions and 47% in those with three or more lesions (hazard ratio, 3.5; P = .01). Rates of overall survival followed the same trend at 98% and 68%, respectively (HR, 13.6; P = .0002).
Likewise, among patients whose FDG uptake did not exceed that of the liver, 2-year rates of progression-free and overall survival were 87% and 100%, compared with 69% and 45% in patients with new focal lesions or slightly, moderately, or markedly greater FDG uptake than the liver (Deauville scores of 4 and 5; P less than .001 for each comparison).
Normalization of FDG-PET/CT after induction also predicted improved survival, Dr. Zamagni said. Two-year progression-free survival rates were 85% among patients who had become PET-negative by the time they began maintenance, but were only 66% among patients who remained PET-positive (HR, 1.5; P less than .01). Rates of overall survival at 2 years were 98% among PET-negative patients and 87% among PET-positive patients (HR, 1.6; P = .03).
The study also confirmed the value of performing FDG-PET/CT at de novo myeloma diagnosis. Strikingly, only 20% of patients with baseline FDG-PET/CT evidence of extramedullary disease at this time point were alive and progression free 2 years later, compared with 81% of those without extramedullary disease (HR, 5.0; P = .001). Once again, the same trend emerged for Deauville scores – 99% of patients with scores of 3 or lower at diagnosis were alive 2 years later, compared with 83% of those who scored 4 or 5 (HR, 5.6; P = .03).
The EMN02 trial included 714 patients with newly diagnosed multiple myeloma who underwent induction with bortezomib-cyclophosphamide-dexamethasone (VCD), followed by either standard-dose intensification therapy with bortezomib-melphalan-prednisone (VMP) or high-dose intensification therapy with melphalan followed by single or double autologous stem cell transplantation. After that, patients either underwent consolidation therapy followed by lenalidomide maintenance therapy or proceeded directly to maintenance. Among the study subgroup of 103 patients, median age was 58 years, 25% of patients had high-risk cytogenetics, and 15% were ISS stage III.
“FDG-PET/CT is by now the preferred imaging technique for evaluating and monitoring response to therapy,” Dr. Zamagni concluded. She and her associates will use data from four other trials to further validate prognostic criteria and more precisely define cutoff points, she said.
Fondazione del Monte di Bologna e Ravenna partially supported the study. Dr. Zamagni had no relevant financial conflicts of interest.