Immune- Checkpoint Inhibitors in Malignant Pleural Mesothelioma: a meta-analysis

Abstract Introduction Malignant pleural mesothelioma (MPM) is an aggressive disease with poor prognosis. Many trials investigated the role of Immune Checkpoint Inhibitors (ICIs) in MPM, with contrasting results. Methods We performed a meta-analysis of clinical trials testing single-agent anti PD-1/PD-L1, anti-CTLA-4 or their combination in MPM patients. Objective response rate (ORR), disease control rate (DCR), 6 months progression-free survival (PFS) and 12 months overall survival (OS) rate were extracted, as well as safety data. The predictive role of PD-L1 was assessed, too. Results We selected 17 studies including 2328 patients. 12 months OS was 53% (95% CI 44–61%), 6 months PFS was 19% (95% CI 13–25%). Both OS and PFS were significantly higher with combined ICIs treatment than single agent anti PD-1/PD-L1 (respectively p < 0.001 and p = 0.006) or anti CTLA-4 (p < 0.001). ORR and DCR were 20% (95% CI 13–27%) and 56% (95% CI 45–67%) and did not significantly differ between combined and single agent ICIs (p = 0.088 and p = 0.058). 12 months OS and 6 months PFS rate did not differ significantly (p = 0.0545 and p = 0.1464) among pre-treated or untreated patients. Combined ICIs treatments have significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1 positive patients have higher ORR, DCR and OS than PD-L1 negative patients. Conclusion ICIs are an efficient treatment option for MPM. Efficacy was independent from treatment line, so customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs, however reliable biomarkers are warranted.