Immune checkpoint inhibitors in mesothelioma

Mesothelioma is an aggressive tumor originating from the mesothelial cells of the pleural or peritoneal cavity. This thesis focuses on the treatment of pleural mesothelioma. For long, chemotherapy has been the standard of care, leading to an overall survival of about 15 months. In this thesis, a phase 2 trial is performed using two checkpoint inhibitors, nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4), to treat recurrent mesothelioma after at least one line of chemotherapy. Of the 34 patients evaluable for response 29% had a partial response and 38% patients had stable disease, so 68% of patients achieved disease control, the primary endpoint. These results exceeded expectations and rejected the alternative hypothesis. In part III translational research was performed on blood samples, pleural biopsies and breath analyses at baseline and after 6 weeks of treatment. In order to find markers of response and try to explain how immunotherapy affects the tumor microenvironment and immune cell subsets of the peripheral blood.