Serum levels of TARC, MDC, IL-10, and soluble CD163 in Hodgkin lymphoma: a SWOG S0816 correlative study

Abstract

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.

Conflict of interest statement

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.

© 2019 by The American Society of Hematology.

Figures

Reproduced with permission from the Cleveland Clinic Foundation (CCF).

Figure 1.

Landmark Kaplan-Meier PFS curves for PET2-negative patients. These curves exclude the 9 patients who were PET3 positive/progressed at time of PET3 or progressed shortly after PET3 assessment using the combined median posttherapy TARC (502.86 pg/mL) and IL-10 (0.2703 pg/mL) levels for these patients as cutoffs, respectively (log-rank test, P = .03). CT, computed tomography.