TY - JOUR
T1 - Serum levels of TARC, MDC, IL-10, and soluble CD163 in Hodgkin lymphoma
T2 - A SWOG S0816 correlative study
AU - Hsi, Eric D.
AU - Li, Hongli
AU - Nixon, Andrew B.
AU - Schöder, Heiko
AU - Bartlett, Nancy L.
AU - LeBlanc, Michael
AU - Smith, Sonali
AU - Kahl, Brad S.
AU - Leonard, John P.
AU - Evens, Andrew M.
AU - Scott, David W.
AU - Rimsza, Lisa M.
AU - Friedberg, Jonathan W.
N1 - Funding Information:
This work is supported by the National Institutes of Health, National Cancer Institute (grants CA180888, CA180819, CA180821, and CA180820) and the Lymphoma Research Foundation.
Funding Information:
Conflict-of-interest disclosure: E.D.H. is on the advisory board of Seattle Genetics, Jazz, and Celgene and has received research funding from Eli Lilly, AbbVie, and Cellerant. A.M.E. is on the advisory boards (with honorarium) of Affimed, Jannsen, Acerta, Bayer, AbbVie, Seattle Genetics, and Novartis and has received research funding from Seattle Genetics and Tesaro. H.S. has received consulting fees from Aileron Therapeutics. D.W.S. has received consulting fees from Celgene and Janssen and research funding from Janssen, Roche/Genentech, and NanoString Technologies. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2019 by The American Society of Hematology
PY - 2019/4/18
Y1 - 2019/4/18
N2 - Serum soluble chemokines/cytokines produced by Hodgkin cells and the tumor microenvironment might be of value as biomarkers in classic Hodgkin lymphoma (cHL). We assessed serum thymus and activation-related chemokine (TARC), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), and soluble CD163 (sCD163) levels at baseline, time of interim fluorodeoxyglucose positron emission tomography (PET), and after therapy in cHL patients treated on S0816, an intergroup phase 2 response-adapted study evaluating escalated therapy for interim PET (PET2)–positive patients (www.clinicaltrials.gov #NCT00822120). Epstein-Barr virus (EBV) status was assessed, and 559 serum samples were evaluated for TARC, MDC, IL-10, and sCD163 by immunoassay. EBV positivity correlated with higher sCD163 and IL-10 levels but lower TARC levels. While baseline biomarker levels were not associated with outcome, sCD163 levels at the time of PET2 were associated with favorable progression-free survival (PFS), adjusting for PET2 status. After therapy TARC, MDC, and IL-10 correlated with PFS and overall survival (OS) on univariable analysis, which remained significant adjusting for international prognostic score. When also adjusting for end-of-therapy PET results, TARC and IL-10 remained significantly associated with shorter PFS and OS. Exploratory analysis in PET2-negative patients showed that elevated posttherapy TARC and IL-10 levels were associated with PFS. Serum cytokine levels correlate with outcome in cHL and should be investigated further in risk-adapted cHL trials.
AB - Serum soluble chemokines/cytokines produced by Hodgkin cells and the tumor microenvironment might be of value as biomarkers in classic Hodgkin lymphoma (cHL). We assessed serum thymus and activation-related chemokine (TARC), macrophage-derived chemokine (MDC), interleukin-10 (IL-10), and soluble CD163 (sCD163) levels at baseline, time of interim fluorodeoxyglucose positron emission tomography (PET), and after therapy in cHL patients treated on S0816, an intergroup phase 2 response-adapted study evaluating escalated therapy for interim PET (PET2)–positive patients (www.clinicaltrials.gov #NCT00822120). Epstein-Barr virus (EBV) status was assessed, and 559 serum samples were evaluated for TARC, MDC, IL-10, and sCD163 by immunoassay. EBV positivity correlated with higher sCD163 and IL-10 levels but lower TARC levels. While baseline biomarker levels were not associated with outcome, sCD163 levels at the time of PET2 were associated with favorable progression-free survival (PFS), adjusting for PET2 status. After therapy TARC, MDC, and IL-10 correlated with PFS and overall survival (OS) on univariable analysis, which remained significant adjusting for international prognostic score. When also adjusting for end-of-therapy PET results, TARC and IL-10 remained significantly associated with shorter PFS and OS. Exploratory analysis in PET2-negative patients showed that elevated posttherapy TARC and IL-10 levels were associated with PFS. Serum cytokine levels correlate with outcome in cHL and should be investigated further in risk-adapted cHL trials.
UR - http://www.scopus.com/inward/record.url?scp=85065022565&partnerID=8YFLogxK
U2 - 10.1182/blood-2018-08-870915
DO - 10.1182/blood-2018-08-870915
M3 - Article
C2 - 30723079
AN - SCOPUS:85065022565
VL - 133
SP - 1762
EP - 1765
JO - Blood
JF - Blood
SN - 0006-4971
IS - 16
ER -