Prognostic value of interim FDG-PET in diffuse large cell lymphoma: results from the CALGB 50303 Clinical Trial

• Published in: Blood Vol. 135; no. 25; pp. 2224 - 2234
• Main Authors: Schöder, Heiko, Polley, Mei-Yin C., Knopp, Michael V., Hall, Nathan, Kostakoglu, Lale, Zhang, Jun, Higley, Howard R., Kelloff, Gary, Liu, Heshan, Zelenetz, Andrew D., Cheson, Bruce D., Wagner-Johnston, Nina, Kahl, Brad S., Friedberg, Jonathan W., Hsi, Eric D., Leonard, John P., Schwartz, Lawrence H., Wilson, Wyndham H., Bartlett, Nancy L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.06.2020; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Clinical Trials and Observations; Cyclophosphamide - administration & dosage; Etoposide - administration & dosage; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse - diagnostic imaging; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Middle Aged; Positron-Emission Tomography; Prednisone - administration & dosage; Prognosis; Progression-Free Survival; Proportional Hazards Models; Prospective Studies; Radiopharmaceuticals; Rituximab - administration & dosage; Vincristine - administration & dosage; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2019003277

As part of a randomized, prospective clinical trial in large cell lymphoma, we conducted serial fluorodeoxyglucose positron emission tomography (FDG-PET) at baseline, after 2 cycles of chemotherapy (interim PET [i-PET]), and at end of treatment (EoT) to identify biomarkers of response that are predictive of remission and survival. Scans were interpreted in a core laboratory by 2 imaging experts, using the visual Deauville 5-point scale (5-PS), and by calculating percent change in FDG uptake (change in standardized uptake value [ΔSUV]). Visual scores of 1 through 3 and ΔSUV ≥66% were prospectively defined as negative. Of 524 patients enrolled in the parent trial, 169 agreed to enroll in the PET substudy and 158 were eligible for final analysis. In this selected population, all had FDG-avid disease at baseline; by 5-PS, 55 (35%) remained positive on i-PET and 28 (18%) on EoT PET. Median ΔSUV on i-PET was 86.2%. With a median follow-up of 5 years, ΔSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] = 0.99; 95% confidence interval [CI], 0.97-1.00; P = .02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P = .03). ΔSUV ≥66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P = .02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P = .09). Visual 5-PS on i-PET did not predict outcome. ΔSUV, but not visual analysis, on i-PET predicted OS in DLBCL, although the low number of events limited the statistical analysis. These data may help guide future clinical trials using PET response-adapted therapy. This trial was registered at www.clinicaltrials.gov as #NCT00118209. •In this phase 3 prospective clinical trial, ΔSUV on i-PET predicted OS in large cell lymphoma.•With appropriate standardization, ΔSUV may be an imaging biomarker that can help guide clinical trials using PET response-adapted therapy. [Display omitted]