Immunotherapy in Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy mainly caused by asbestos exposure. Basic research about the immune suppressive tumor microenvironment in MPM has suggested that MPM might be a good candidate for immune therapy. Immunocheckpoint inhibitors have shown some promising results. A phase Ib trial with pembrolizumab, an antibody specific for the programmed cell death 1 protein (anti-PD-1), showed efficacy in patients with programmed death-ligand 1 (PD-L1)-positive MPM. Among 25 patients tested, 5 patients (20%) achieved a partial response. A Japanese group evaluated the efficacy and safety of nivolumab, an anti-PD-L1 antibody, for patients with advanced MPM in a phase II study. Ten (29%) patients showed an objective response. Based on those results, nivolumab was approved in Japan for unresectable recurrent MPM. A phase III randomized study was conducted to compare nivolumab plus ipilimumab to platinum doublet chemotherapy as a first-line therapy in unresectable MPM. The primary endpoint, overall survival (OS), was significantly improved in the nivolumab plus ipilimumab group. Cellular therapies and cancer vaccines are limited by many challenges; therefore, improvements to overcome these difficulties are urgently warranted. Further research is needed, including large-scale clinical trials, to clarify the utility and safety of immunotherapy in MPM.