Percist-Derived Metabolic Volume Response Predicts Overall And Progression-Free Survival In Patients With Malignant Pleural Mesothelioma Treated With Pembrolizumab

243 Objectives: Despite promising response rates in phase 1b and 2 clinical trials, immune checkpoint inhibition (ICI) with pembrolizumab for the treatment of malignant pleural mesothelioma (MPM) did not result in survival benefit in the PROMISE-meso trial compared to 2nd-line chemotherapy. Due to lack of validated imaging response criteria, responder-subgroups with potential survival benefit have not yet been identified. Here, we assess the predictive value of PET metabolic response in patients undergoing four cycles of high-dose pembrolizumab (10 mg/kg, d1, q2w) considering the KEYNOTE-028 trial procedure for chemotherapy-resistant malignant pleural or peritoneal mesothelioma.\n Methods: RECIST v1.1, mRECIST, PERCIST (using SULpeak, MTV and TLG) response assessment criteria were used separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall Survival (OS) of responders were compared to non-responders using Kaplan-Meier methods and log-rank comparisons. Fishers-exact testing was used to compare PD-L1e expression status of responders vs.non-responders.\n Results: Twenty-seven patients had [18F]-FDG-PET/CT imaging at baseline and after four cycles of pembrolizumab.. Response rates were 7%, 7%, 30%, 30% and 33% based on RECIST v1.1, mRECIST, PERCIST, MTV and TLG response criteria, respectively. Regarding PFS, only MTV and TLG response groups showed a significant different survival (p \u003c 0.01, respectively). Regarding OS, only a reduction of MTV ≥30% predicted prolonged survival (p \u003c 0.01). PD-L1 expression could not be associated with response rates or survival.\n Conclusions: PERCIST-derived metabolic volume response predicts survival in pretreated patients with malignant mesothelioma receiving high-dose pembrolizumab. These results warrant inclusion of PET response assessment in future clinical trials and routine practice.