TY - JOUR
T1 - Prognostic value of interim FDG-PET in diffuse large cell lymphoma
T2 - Results from the CALGB 50303 clinical trial
AU - Schöder, Heiko
AU - Polley, Mei Yin C.
AU - Knopp, Michael V.
AU - Hall, Nathan
AU - Kostakoglu, Lale
AU - Zhang, Jun
AU - Higley, Howard R.
AU - Kelloff, Gary
AU - Liu, Heshan
AU - Zelenetz, Andrew D.
AU - Cheson, Bruce D.
AU - Wagner-Johnston, Nina
AU - Kahl, Brad S.
AU - Friedberg, Jonathan W.
AU - Hsi, Eric D.
AU - Leonard, John P.
AU - Schwartz, Lawrence H.
AU - Wilson, Wyndham H.
AU - Bartlett, Nancy L.
N1 - Funding Information:
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Institutes of Health, National Cancer Institute (U10CA180821, U10CA180882) to the Alliance for Clinical Trials in Oncology and U10CA180791, U10CA180833, U10CA180850, and UG1CA189960 (https://acknowledgments. alliancefound.org). Scientific and financial support for the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium project ?FDG-PET in Lymphoma? and the current study were made possible through funding to the FNIH by Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Leukemia & Lymphoma Society, Merck, Pfizer, and Wyeth (HHSN261200800001E). This research was also funded in part through a National Institutes of Health National Cancer Institute Cancer Center Support Grant (P30 CA008748).
Funding Information:
Conflict-of-interest disclosure: H.S. was a consultant to Aileron Therapeutics until June 30, 2018 (unrelated to current work). A.D.Z. serves or has served as a consultant for Genentech/Roche, Gilead, Celgene, Janssen, Amgen, Novartis, Adaptive Biotechnology, and Verastem; he serves on the advisory board of MorphoSys, Gilead, Genentech, Abbvie, and AstraZeneca Pharmacyclics and receives research support from MEI Pharmaceuticals, Roche, Gilead, and Beigene; he also serves as the DMC Chair for Beigene. N.W.-J. serves or has served on the advisory boards for Bayer, Gilead, ADC Therapeutics, and Janssen. B.K. serves as a consultant for Genentech and Roche, and receives research funding from Genentech. J.F. has received honoraria from Bayer and Ascerta for data and safety monitoring committee activities. E.H. receives research support from Eli Lilly & Co. and Abbvie and serves on the honoraria advisory boards of Seattle Genetics, Celgene, and Jazz Pharmaceuticals. J.P.L. serves or has served as a consultant for Sutro, Bayer, Gilead, AstraZeneca, Celgene, Roche/Genentech, ADC Therapeutics, Sandoz, Karyopharm, Miltenyi, Novartis, Biotest, Merck, Morphosys, Beigene, Nordic Nanovector, BMS, Akcea Therapeutics, Epizyme, and MEI Pharma. L.H.S. has received third-party payments from Merck, Roche, and Pfizer for participating on data safety monitoring and endpoint committees and has served as a consultant for Boehringer and Imaging Endpoints. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/6/18
Y1 - 2020/6/18
N2 - 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 [DSUV]). Visual scores of 1 through 3 and DSUV ‡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 DSUV on i-PET was 86.2%. With a median follow-up of 5 years, DSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] 5 0.99; 95% confidence interval [CI], 0.97-1.00; P 5.02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P 5.03). DSUV ‡66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P 5.02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P 5.09). Visual 5-PS on i-PET did not predict outcome. DSUV, 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.
AB - 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 [DSUV]). Visual scores of 1 through 3 and DSUV ‡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 DSUV on i-PET was 86.2%. With a median follow-up of 5 years, DSUV, as continuous variable, was associated with progression-free survival (PFS) (hazard ratio [HR] 5 0.99; 95% confidence interval [CI], 0.97-1.00; P 5.02) and overall survival (OS) (HR, 0.98; 95% CI, 0.97-0.99; P 5.03). DSUV ‡66% was predictive of OS (HR, 0.31; 95% CI, 0.11-0.85; P 5.02) but not PFS (HR, 0.47; 95% CI, 0.19-1.13; P 5.09). Visual 5-PS on i-PET did not predict outcome. DSUV, 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.
UR - http://www.scopus.com/inward/record.url?scp=85086694782&partnerID=8YFLogxK
U2 - 10.1182/blood.2019003277
DO - 10.1182/blood.2019003277
M3 - Article
C2 - 32232481
AN - SCOPUS:85086694782
SN - 0006-4971
VL - 135
SP - 2224
EP - 2234
JO - Blood
JF - Blood
IS - 25
ER -