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Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. In previously treated patients ( p), no-randomized studies of immunotherapy (ICI) have demonstrated activity, and Checkmate 743 demonstrated survival benefit of ICI in first line with some differences according to histology. The objective of this study is to characterize the impact of ICI use on survival in p diagnosed with MPM at our institution. Methods: We review 189 MPM p diagnosed at Vall d'Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient's characteristics: median age 68 years (y) (45-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 74%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed) and 19 p were treated in clinical trials in first line. Median progression free survival (PFS) was 4.4 months (m;CI95% 3.1-5.4). Median survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio >5 and treatment with cisplatin vs. carboplatin were associated with significant improvements in OS. In second line 27 p were treated with ICI in clinical trials. Median OS for p treated with ICI was 22.6 m (95%CI 11.1-34). No differences in PFS and OS for p treated with ICI were detected according to histology. Median PFS 2.7 m in epithelioid and 3 m in no-epithelioid (HR0.7, p = 0.43 CI95% 0.3-1.7) and OS 28.3 m in epithelioid and 13.8 m in noepithelioid (HR3.4 p = 0.01 CI95% 1.3-8.7). When we considered the OS of p treated with ICI from the time of initiation of the ICI, the median OS for epithelioid p was 12.4 m vs. 6.18 m for no epithelioid (HR2.1, p = 0.09 CI95% 0.8-5.2). Conclusions: In our series, ICI was an acceptable option for previously treated MPM patients. We confirmed histology is a prognostic factor with better OS for p with epithelioid tumors. However, we could did not demonstrate histology is a predictive factor for efficacy of ICI.