The objective of this post–hoc correlative analysis was to assess the relationships between baseline and longitudinal PET–CT metrics and treatment outcomes, including response assessments, progression–free survival, and overall survival, in patients with relapsed or refractory classical Hodgkin lymphoma treated with tislelizumab in the LYSA phase 2 TIRHOL study. The analysis also examined relationships between tislelizumab pharmacokinetics and baseline clinical and PET–CT characteristics.

In the TIRHOL study, patients received tislelizumab every 3 weeks until progressive disease, unacceptable toxicity, or study withdrawal, with disease response assessed by investigators every 12 weeks using Lugano 2014 PET–CT criteria. For this analysis, baseline and follow–up PET–CT scans were evaluated post–hoc by a central, independent reviewer. Relationships were assessed between baseline PET-CT metrics (TMTV4, TLG4, Dmax4, SUVmean, and SUVmax) and response assessments, progression-free (PFS), and overall survival (OS). The longitudinal evolution of TMTV4 and SUV during tislelizumab therapy was also examined. Tislelizumab pharmacokinetics profiles (cycle 1 post-dose and cycle 2 pre-dose concentrations) were evaluated against baseline clinical and PET-CT characteristics.

Baseline and follow–up PET–CT images were available for central review in 37 of 45 treated patients. Based on central review, the overall response rate was 70%, with complete metabolic response (CMR) in 40% and partial metabolic response (PMR) in 30%. At Week 12, CMR, PMR, and no metabolic response (NMR) were observed in 27%, 35%, and 35% of patients, respectively. Patients with best metabolic response of CMR, PMR and NMR had 1-year PFS rates of 60%, 26%, and 8%, and 1-year OS rates of 100%, 100%, and 77%, respectively. Median baseline PET-CT metrics were comparable across Week 12 and best metabolic response categories and were comparable between patients with PFS or OS events and those who remained event-free. Longitudinal evaluations of TMTV4 and SUV showed a rapid decrease of values at first evaluation for patients with CMR and PMR at Week 12. The patterns of TMTV4 and SUV variations during tislelizumab treatment differed between patients with best metabolic response of CMR, PMR, and NMR. No differences in pharmacokinetic results were observed based on key baseline categorical variables (sex, age, B-symptoms, cohort 1/2, Ann Arbor stage, bulk, refractory vs relapse, IPS score, TMTV4, albumin level).