Immune checkpoint inhibitors in advanced malignant peritoneal mesothelioma: Clinical insights, immunopathologic profiling, and prognostic implications from a single-center study.

e14665 Background: Malignant peritoneal mesothelioma (MPM) is a rare malignancy of the peritoneum. In patients with advanced disease, therapeutic options are limited, and prognosis is usually poor. While the role of immune-checkpoint inhibitors (ICI) in MPM is evolving, clinical data is scarce and there are currently no biomarkers to predict response to ICI therapy in this population. Methods: Patients treated at the Sheba Medical Center between 2016-2022 have been examined with the aim of delineating the clinical and immunopathologic characteristics of MPM, including programmed-death ligand-1 (PDL-1) status. Results: Forty-two patients with MPM were treated at Sheba during the study period. Eight patients (19%) have received immunotherapy as a single treatment in our cohort, all as ≥2 line of treatment. Of these patients, 3 patients (37.5%) had complete response (CR) or partial response (PR) as their best response, 3 patients (37.5%) had stable disease (SD), and 2 patients (25%) had progressive disease. Median overall survival (OS) among responding patients (CR/PR) and patients with clinical benefit (CR/PR/SD) were 6.8 years and 5.2 years, respectively, noticeably higher than the median OS for MPM (2.5 years). PDL-1 status was available for 23 patients: 17/23 (74%) had negative PDL-1 status and 6/23 (26%) had positive PDL-1 status. No correlation was observed in PDL-1 status among patients experiencing clinical benefit from treatment with ICIs. Conclusions: ICI therapy could be considered as a reasonable option for second-line therapy and beyond for MPM, with selected patients who may substantially benefit from these treatments. PDL-1 status did not correlate with treatment benefit, which highlights the limitation of this biomarker as a predictor of response in MPM patients.