Abstract T051

Serum TARC Dynamics Correlate with Clinical Response and Metabolic Tumor Volume During Anti-PD1-Based First-Line HL Treatment in The GHSG Phase II NIVAHL Trial

Background: Serum Thymus and Activation Regulated Chemokine (TARC) is a well-established tumor cell derived biomarker for monitoring early treatment response in classic Hodgkin lymphoma (cHL), offering higher positive predictive value compared to interim FDG-PET imaging. However, data on TARC in patients receiving anti-PD1-based first-line treatment is limited. To our knowledge, this is the first study correlating TARC dynamics with metabolic tumor volume (MTV) and clinical response during either sequential or concomitant nivolumab and doxorubicin, vinblastine, and dacarbazine (N-AVD) first-line treatment of early-stage unfavorable cHL patients.

Methods: Patients in the prospective randomized GHSG NIVAHL phase II trial were evaluated for early treatment response (RE2) after 2 × N-AVD (arm A) or four nivolumab (N) infusions (arm B), respectively (NCT03004833). This study included all 78 NIVAHL patients with informed consent and serum samples available at baseline and at least one additional timepoint: after 1 week, at RE2, post chemotherapy and/or post 30Gy IS-RT. TARC levels were measured using a standardized ELISA, with a predefined positivity threshold of >1000 pg/ml, while being blinded to treatment and response. For longitudinal analysis, only patients with elevated baseline TARC were included and were correlated with MTV.

Results: TARC levels were positive in 71/78 patients (91%) at baseline, with a median level of 14,830 pg/ml (range 203 - 339,000 pg/ml). Baseline TARC levels significantly correlated with baseline MTV (Spearman r=0.41, p =.007). Already after 1 week of treatment, a sharp decline in TARC levels was observed in both treatment groups (Figure 1). At the RE2, only 3% and 19% of cases remained TARC positive in arm A (2 × N-AVD) and arm B (4 × N), respectively, demonstrating early deep responses in the vast majority of patients, including patients treated with nivolumab monotherapy. Notably, TARC negativity was observed in 12 out of 18 cases (67%) with a positive PET at RE2 and 4 out of 4 cases (100%) at end of treatment. All did not experience a relapse with a median follow-up of 41 months.

Conclusion: Serum TARC levels correlate with MTV and treatment response in cHL patients receiving anti-PD1-based first-line treatment. Importantly, TARC negativity is achieved very early also during nivolumab monotherapy and associated with excellent outcomes despite interim or end-of-treatment PET positivity.