Background: Treatment guidance based on interim response as determined by PET imaging has become standard of care in classic Hodgkin lymphoma (cHL). However, the positive predictive value of interim PET (PET-2) is limited resulting in a significant proportion of patients being overtreated. The tumor cell specific serum biomarker Thymus and Activation Regulated Chemokine (TARC) might aid in early response assessment. The aim of the current study is to investigate the prognostic value of interim TARC (TARC-2) in patients treated in the German Hodgkin Study Group HD16 and HD18 trials.
Methods: Patients with cHL and available serum samples from HD16 and HD18 trials that were treated without PET-2 treatment adaptation were included. TARC was measured by standard ELISA and levels > 1000 pg/ml were considered positive as previously defined. The primary outcome measure was progression free survival (PFS). Hazard Ratios were obtained by Cox regression analysis adjusted for age, sex, and trial if applicable. This study was performed on behalf of the consortium for minimal residual disease in cHL.
Results: A total of 278 patients with measurable disease at baseline were included (76 from HD16 and 202 from HD18). At baseline 51 (67%) of early favorable patients and 176 (87%) of advanced stage patients were TARC positive. After 2 cycles, 3 (6%) and 27 (15%) of patients in the HD16 and HD18 trial remained TARC-positive, respectively. TARC-2 was negative in 91% of PET-2 negative patients (n=153) as well as in 76% of PET-2 positive patients (n=44). TARC-2 positive patients had significantly worse 5y-PFS of 75% compared to 90% in TARC-2 negative patients in the entire cohort. PET-2 positive patients had a non-significant lower PFS of 84% vs 89% in PET-2 positive patients. In the combined analysis, PET-2 positive / TARC-2 negative patients had a 5-year PFS of 91%, not different from the PET-2 negative patients (Figure 1). However, PET-2 positive / TARC-2 positive patients (n=14) had a 5-year PFS of only 61% (HR = 3.84 (1.41 – 10.50)).
Conclusion: We confirmed the adverse prognostic value of TARC-2 in an independent large non PET adapted cohort. Remarkably, TARC-2 could identify a subgroup of >75% of PET-2 positive patients that have excellent outcome, while at the same time identifying a group of double positive patients that are at high risk of treatment failure. The integration of TARC in response assessment can further decrease overtreatment in cHL.
Wouter J. Plattel, Janina Jablonski, Mia Lohmann, Bastian Von Tresckow, Anna Sureda, Michiel Pegtel, Josée M. Zijlstra, John Radford, Bart-Jan Kroesen, Lydia Visser, Michael Fuchs, Peter Borchmann, Arjan Diepstra, Sven Borchmann