Clinical activity of pembrolizumab monotherapy in diffuse malignant peritoneal mesothelioma

8557 Background: Among patients with malignant mesothelioma, pembrolizumab has demonstrated activity in diffuse pleural mesothelioma (DPM), with limited data available for those with diffuse malignant peritoneal mesothelioma (DMPM). DMPM represents a clinically distinct entity from DPM and disease specific outcomes data is needed. We present real world data on the efficacy of pembrolizumab in DMPM. Methods: In this retrospective study, we identified patients with DMPM treated with pembrolizumab at two tertiary care cancer centers between 1/1/2009 and 1/1/2021. Clinicopathologic features were annotated. Median progression free survival (mPFS) and median overall survival (mOS) were calculated using Kaplan-Meier curves. Best overall response rate (BOR) was determined using RECIST 1.1 criteria. Association of partial response with disease characteristics was evaluated using Fisher’s exact test. Results: We identified 24 patients with DMPM who received pembrolizumab (median age 62 years, 63% never smokers, 58% female, 75% had epithelioid histology). All patients received systemic chemotherapy prior to pembrolizumab (median prior lines of therapy: 3). BOR was 17% (3 partial responses, 10 stable disease, 5 progressive disease, 6 lost to follow-up). With a median follow up time of 29.2 months, mPFS was 4.9 months and mOS 20.9 months from pembrolizumab initiation. Three patients experienced PFS of > 2 years. Among the 14 patients who underwent next generation sequencing of tumor tissue, there were 8 somatic BAP1 alterations. Among the 17 patients tested for PDL1, 6 had positive PDL1 expression (1-80%). There was no association between partial response and presence of a BAP1 somatic alteration (p = 0.453), PDL1 positivity (p = 0.7) or non-epithelioid histology (p = 0.55). Conclusions: Pembrolizumab is active in a PDL1 unselected cohort of patients with DMPM. The overall response rate of 17% and mPFS of 4.9 months in this 75% epithelioid histology cohort warrants further investigation to identify those most likely to respond to immunotherapy, especially among epithelioid histology.