Mid-Treatment Plasma Levels of Thymus Activated and Regulated Chemokine (TARC) Predict Treatment Outcome In Classical Hodgkin Lymphoma Patients

Thymus and Activation Regulated Chemokine (TARC) is highly expressed by the Hodgkin Reed Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (cHL) in the vast majority of patients. This chemokine is released in the circulation and may serve as a cHL specific biomarker. We and others showed high serum levels of TARC before start of treatment and a significant decrease in serum TARC levels after treatment. The aim of the current study is to relate plasma TARC levels during treatment with response as observed by FDG-PET imaging in cHL patients.

Sixty-three newly diagnosed cHL patients from the University Medical Center Groningen were included from 2005 until 2009. Patients were treated according to clinical trial (EORTC) or hospital protocols: 1^st line treatment consisted of ABVD chemotherapy with or without involved node radiotherapy for stage I/II and ABVD or EscBEACOPP/BEACOPP chemotherapy for other stages. Plasma was collected before treatment and ideally also before start of every chemotherapy cycle, with at least a sample concurrent with mid-treatment FDG-PET evaluation and at completion of treatment. Plasma TARC levels were evaluated by ELISA. TARC expression in HRS cells was determined by immunohistochemistry (IHC) on tissue samples.

TARC staining was observed in the HRS cells in 95% of patients. Patients with negative TARC staining did not have elevated pre-treatment plasma TARC levels and were excluded from further analysis. Pre-treatment plasma TARC levels in stage II-IV disease were significantly higher compared to stage I disease (p < .001). Patients with bulky disease had significantly higher TARC values compared to patients without bulky disease (p = .04). Mid-treatment TARC was significantly elevated in 2 out of 54 patients with an available plasma sample (Figure 1). Mid-treatment FDG-PET was positive in 13/53 patients. Two patients had persistent mid-treatment FDG-PET activity in >2 nodes and these 2 patients were the only two patients with persistent high mid-treatment TARC. The other 11 mid-treatment FDG-PET positive patients only had residual FDG-PET positivity in 1 or 2 nodes and TARC was normalized in all 11 patients. Two of these 11 patients switched to EscBEACOPP dictated by the mid-treatment FDG-PET result since they were treated in the experimental arm of the EORTC H10 trial, while the 2 patients with >2 mid-treatment FDG-PET positive nodes and high TARC did not switch since they were treated in the standard arm of this trial. End-treatment TARC was significantly elevated in 2 out of 58 patients. 4/13 mid-treatment FDG-PET positive patients remained FDG-PET positive at end-treatment evaluation. The two patients with persistent activity in >2 nodes and high TARC at mid-treatment evaluation had progressive disease at end-treatment evaluation and TARC levels remained high. Of the 11 patients with mid-treatment FDG-PET positivity and low mid-treatment TARC, 9 became FDG-PET negative. Two patients (one of those who switched to EscBEACOPP) still had residual FDG-PET activity in the same spots at end-treatment evaluation while TARC remained low. The other patient proceeded to second line treatment but remained FDG-PET positive. However, both patients did not progress during 6 months follow-up without further treatment. Of note: after one cycle of first line chemotherapy we could already observe the same plasma TARC dynamics as observed at mid- and end-treatment evaluation (n=42, Figure 1).

Figure 1.

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Plasma TARC dynamics before, during and after 1^st line treatment in 63 newly diagnosed cHL patients.

Figure 1.

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Plasma TARC dynamics before, during and after 1^st line treatment in 63 newly diagnosed cHL patients.

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Mid-treatment plasma TARC levels outperformed mid-treatment FDG-PET imaging in predicting response to therapy in primary cHL patients. Moreover, TARC levels after one chemotherapy cycle could already predict final response to treatment. Evaluation of TARC dynamics before and during treatment in future clinical trials is needed to confirm the prognostic value of plasma TARC in cHL patients.

No relevant conflicts of interest to declare.