AR8 - PD-L1 Expression is Altered in Malignant Peritoneal Mesothelioma Patients after Chemotherapy and HIPEC

Background Malignant peritoneal mesothelioma (MPM) is a rare disease of the serosal membrane in the peritoneal cavity. Systemic chemotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are treatment modalities utilized in the multidisciplinary management of this disease. In patients with MPM, tumor expression of programmed death-ligand 1 (PD-L1) protein is associated with a higher response rate to anti-PD1 therapy after first line therapy. Alterations in PD-L1 expression after chemotherapy have been shown in other tumor histologies, but the effect of both chemotherapy and HIPEC on the immune microenvironment of MPM tumors remains unclear. We sought to characterize PD-L1 expression in MPM tumors before and after HIPEC and systemic chemotherapy. Methods A retrospective review identified two parallel groups of patients with MPM who underwent HIPEC at our institution from 2017-2019. Group 1 underwent laparoscopy followed by systemic chemotherapy and then CRS/HIPEC, while Group 2 underwent laparoscopic HIPEC followed by systemic chemotherapy and then CRS/HIPEC. Immunohistochemistry was performed on pre- and post-treatment (CRS/HIPEC) tumor tissue and scored for PD-L1 expression (% of cells). Results A total of 25 patients were initially identified, of which 6 patients were allocated to the two groups. All patients received platinum-based systemic chemotherapy. HIPEC was performed with Mitomycin C 30 mg at time 0 and 10 mg at time 60 for a total duration of 90 minutes. Median peritoneal cancer index (PCI) was 35 (range 27 – 39). All patients had epithelioid histologic subtype. Data regarding microsatellite stability was available for three patients, all of whom were microsatellite stable. Complete data on pre- and post-treatment PD-L1 expression was available in five of the six patients. In all of the patients, PD-L1 expression was altered after multimodality treatment (Table 1). Conclusion PD-L1 expression in MPM tumors is altered after receiving systemic chemotherapy as well as HIPEC. This may be representative of tumor heterogeneity, but likewise suggests that analyzing PD-L1 expression at different time points during treatment of patients with MPM may be of potential value to better understand the role of PD-1 inhibition and immunotherapy in this patient population. Table 1. Clinicopathologic characteristics of patients who underwent multimodality management of malignant peritoneal mesothelioma. Group 1: Laparoscopy -> Systemic Chemotherapy -> CRS/HIPEC Patient Pre-Treatment PD-L1 (%) Post-Treatment PD-L1 (%) Pre-Treatment PCI Histology Grade 1 0 20 39 epithelioid 1 2 60 20 27 epithelioid 2 3 0 10-20 33 epithelioid 1 Group 2: Laparoscopic HIPEC -> Systemic Chemotherapy -> CRS/HIPEC Patient Pre-treatment PD-L1 (%) Post-Treatment PD-L1 (%) Pre-Treatment PCI Histology Grade 1 5 20 37 epithelioid 2 2 85-90 1-2 33 epithelioid 1 3 Unknown 0 39 epithelioid 3