Abstract P133

Serum TARC monitoring during routine follow-up leads to early diagnosis of relapse in classic Hodgkin lymphoma

Background: Thymus and Activation Regulated Chemokine (TARC, or CCL-17) is a chemokine that is specifically excreted by Hodgkin Reed-Sternberg cells in classic Hodgkin lymphoma (cHL). TARC is excreted in extremely high quantities that result in elevated serum levels in ~90% of cHL patients at diagnosis. TARC levels correlate with metabolic tumour volume (MTV) and elevated levels can precede clinical symptoms and diagnosis up to 6 years. The aim of the current study was to evaluate whether serial serum TARC measurements during routine follow-up of cHL patients achieving a complete response after first-line treatment enables early detection of relapse.

Methods: Our cohort included 162 patients with cHL who were treated at the University Medical Centre Groningen between 2005 and 2022 and who achieved a complete metabolic response. Serum samples were collected before, during and at the end of treatment and during routine follow-up every 3-6 months for up to 5 years post-treatment. TARC levels were analysed either retrospectively (blinded to disease status) or prospectively using routine diagnostic procedures by ELISA. TARC levels >1000 pg/ml were defined as positive, as previously described. MTV was quantified on FDG-PET scans at relapse using 3D Slicer with MUST-segmenter and SUV4.0 as threshold and was correlated with TARC.

Results: At a median follow-up of 36 months, 148/162 patients (91%) remained in remission. A total of 944 samples were collected of these patients. 96% of these samples were TARC negative, while 3.8% were elevated (Figure 1A). Most of these were single time-point elevations and were related to eczema or other recognizable immune conditions. Of the 14 patients that were diagnosed with a histologically confirmed relapse, 11 patients (79%) had elevated TARC levels. TARC elevation preceded clinical symptoms and was the first sign of relapse in 9/11 (82%) of these cases. (Figure 1B). Sensitivity, specificity, positive and negative predictive value of TARC for cHL relapse were 79%, 92%, 48% and 98% respectively. At relapse, TARC levels strongly correlated with MTV (Spearman r = 0.70, p = 0.025).

Conclusion: In conclusion, integrating serum TARC monitoring into routine follow-up results in biochemical detection of relapse in 79% of cases, often preceding clinical symptoms. TARC levels at relapse strongly correlate with MTV. We suggest integrating serum TARC monitoring during routine follow-up of cHL patients to enable early detection of relapse.

Authors

Sophie Teesink, Lydia Visser, Kylie Keijzer, Bart-Jan Kroesen, Marcel Nijland, Anke van den Berg, Arjan Diepstra, Wouter J. Plattel