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Serum levels of TARC, MDC, IL10 and soluble CD163 in Hodgkin lymphoma: a SWOG S0816 correlative study

Eric D. Hsi, Hongli Li, Andrew B. Nixon, Heiko Schöder, Nancy L. Bartlett, Michael LeBlanc, Sonali Smith, Brad S. Kahl, John P. Leonard, Andrew M. Evens, David W. Scott, Lisa M. Rimsza and Jonathan W. Friedberg

Key points

  • Elevated post-therapy IL10 and TARC levels were associated with shorter survival, after adjusting for PET results in S0816.

  • Exploratory analysis suggest IL10 and TARC levels are associated with PFS in PET-negative patients in S0816.

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 TARC, MDC, IL10, and soluble CD163 (sCD163) levels at baseline, time of interim fluorodeoxyglucose positron emission tomography (FDG-PET), and post-therapy in cHL patients treated on S0816, an intergroup phase 2 response-adapted study evaluating escalated therapy for interim PET(PET2)-positive patients (ClinicalTrials.gov Identifier: NCT00822120). Epstein-Barr virus (EBV) status was assessed and 559 serum samples were evaluated for TARC, MDC, IL10, and sCD163 by immunoassay. EBV-positivity correlated with higher sCD163 and IL10 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. Post-therapy TARC, MDC, and IL10 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 IL10 remained significantly associated with shorter PFS and OS. Exploratory analysis in the PET2-negative patients showed that elevated post-therapy TARC, together with IL10 levels, were associated with PFS. Serum cytokine levels correlate with outcome in cHL and should be investigated further in risk-adapted cHL trials.

  • Submitted August 22, 2018.
  • Accepted January 22, 2019.