BACKGROUND Plasma or serum CC-chemokine ligand 17 (CCL17) / Thymus and Activation Regulated Chemokine (TARC) is a highly specific biomarker for classical Hodgkin lymphoma (cHL) disease activity. Serial TARC levels correlate with treatment response as early as after one cycle of chemotherapy. In the current study we compared predictive value of mid-treatment TARC with mid-treatment FDG-PET for modified progression free survival (mPFS) in primary cHL patients.
PATIENTS AND METHODS: Serial serum or plasma samples were prospectively obtained from 112 newly diagnosed (65 early stage and 57 advanced stage) cHL patients. Patients were mainly treated with ABVD or eBEACOPP based treatment regimens. TARC levels were quantified using ELISA. FDG-PET results were quantified and reassessed according to the Lugano classification including Deauville five point score. Events for mPFS were scored in case of death due to any cause, progression of cHL or start of second line treatment. Patients without elevated TARC at pre-treatment and patients with active atopic dermatitis were excluded for survival analysis on TARC.
RESULTS Median follow-up was 45 months for the entire cohort. Out of 112 patients, 103 (92%) achieved a complete remission, 8 patients (7%) had a partial response and one patient (1%) had progressive disease. Of 92 patients with a mid-treatment FDG-PET scan 16 (17%) were positive (Deauville ≥4). Mid-treatment FDG-PET positive patients had significantly reduced mPFS compared to mid-treatment FDG-PET negative patients (56% versus 93% at 3 years, p<.001, Figure 1A). Pre-treatment TARC levels were elevated in 100/112 patients (89%) of which two patients had active atopic disease. Of 92 patients with a mid-treatment plasma or serum sample, TARC was elevated (>900 pg/ml) in 8 (9%). mPFS at 3-years was 25% for patients with high mid-treatment TARC and 92% for patients with low mid-treatment TARC levels (p<.001, Figure 1B). Elevated mid-treatment TARC levels were associated with mid-treatment Deauville score of 5. In multivariate analysis both mid-treatment FDG-PET and mid-treatment TARC independently predicted for mPFS.
CONCLUSION Elevated levels of TARC at mid-treatment are highly predictive for inferior mPFS. Both negative and positive predictive value of mid-treatment TARC are at least as good or even better than mid-treatment FDG-PET imaging. TARC might serve as a substitute for mid-treatment FDG-PET imaging in future response evaluation.
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