Abstract P042

Association of quantitative FDG-PET parameters and serum TARC with outcome in advanced classic Hodgkin lymphoma: A biomarker analysis of the EORTC-1537-COBRA trial

Background: In classic Hodgkin lymphoma (cHL), FDG-PET is used for staging and response assessment using Deauville Score (DS). However, the positive predictive value of an interim PET (iPET) DS 4 is restricted. Quantitative PET parameters such as metabolic tumour volume (MTV), provide objective measures of tumour burden. Serum Thymus and Activation-Regulated Chemokine (sTARC), highly expressed by Hodgkin Reed-Sternberg cells, has emerged as a biomarker for disease monitoring. We evaluated the association between quantitative PET parameters, sTARC, and outcome in the EORTC-1537-COBRA trial.

Methods: The trial enrolled advanced stage cHL patients. Baseline and early interim FDG-PET-scans were centrally reviewed and scored using DS. After one cycle of A‐AVD, patients with a positive iPET (DS 4-5) were escalated to intensified treatment. Quantified PET parameters were derived by semiautomatic segmentation. TARC was measured in serum by ELISA at multiple timepoints. Elevated sTARC was predefined as >1000 pg/ml. Associations were assessed using Pearson correlation and Kaplan Meier estimates were performed to analyse correlation with modified progression-free survival (mPFS), the primary endpoint.

Results: At baseline, 95% of evaluable patients showed elevated sTARC levels, resulting in 127 patients included in this analysis. sTARC declined rapidly after one cycle of A-AVD, with only 24% showing elevated sTARC at interim assessment. In contrast, 42% of patients remained iPET-positive according to DS. Using a SUV4.0 threshold, residual MTV was detected in 7% of patients (table 1). Residual MTV did not identify a subgroup of total patients with a significantly worse mPFS. Elevated sTARC correlated with adverse mPFS. Available follow-up data indicate that sTARC remained normalized in 99 of 111 (89%) patients without a mPFS event. Sequential follow-up data will be presented at the conference.

Conclusion: Despite a substantial proportion of patients remaining iPET-positive based on DS, residual measurable MTV was uncommon after one cycle of A-AVD. No significant association with worse outcome was found, probably due to treatment intensification in iPET-positive patients. Available data indicate that sTARC remained normalized in most patients without a mPFS event during follow-up and sTARC levels were associated with outcome. These findings suggest that sTARC complements PET and support further investigation of sTARC-guided disease monitoring in cHL.