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.

Highlights

  • Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy, which is mainly caused by asbestos exposure [1]

  • We summarize recent studies on immunotherapy for MPM

  • Mansfield et al reported that programmed death-ligand 1 (PD-L1) was expressed in approximately 42 of 106 MPM specimens, and that PD-L1 expression was significantly correlated with poor survival (OS: 5 months in a PD-L1-positive group vs. 14.5 months in a PD-L1-negative group) [14]

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Summary

Introduction

Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy, which is mainly caused by asbestos exposure [1]. The benefit of surgical resection is controversial, because only a minority of patients with MPM meets the criteria for surgery, and it is unrealistic to assume that surgery will achieve a complete tumor resection without a micro residual tumor. Systemic chemotherapy with platinum plus pemetrexed is the recommended first-line systemic therapy for advanced MPM. Immunocheckpoint inhibitors (ICIs) have achieved great success in treating several cancer types [4–7]. Basic research about the immune-suppressive tumor microenvironment in MPM has suggested that MPM might be a good candidate for immune therapy [8, 9]. Advances in Precision Medicine Oncology reported to predict a favorable prognosis after a resection of MPM [10]. ICIs have shown promising results for patients with MPM. We summarize recent studies on immunotherapy for MPM

Anti-cytotoxic T-lymphocyte antigen 4 antibody
Anti-PD-L1 antibody
Pembrolizumab
Nivolumab
Combination therapy with ICIs
Vaccine
Dendritic cell therapy
Chimeric antigen receptor T-cell therapy
Conclusion
Findings
Conflict of interest
Full Text
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