Pathological complete response in a patient with pleural mesothelioma treated with immunotherapy: a case report.

The role of immunotherapy in the multimodal treatment for pleural mesothelioma (PM) is still under investigation, particularly in the preoperative setting. Pathological complete response (pCR) has been previously described after chemotherapy and immunotherapy; however, there is no prior experience reported with immunotherapy alone before surgery. We report the case of a 58-year-old male with biphasic PM treated with immunotherapy, resulting in a major clinical partial response. Following a multidisciplinary evaluation between thoracic surgeons, medical oncologists, pathologists, radiologists and radiation oncologists, the patient underwent surgery with radical intent through a right extended pleurectomy/decortication (eP/D). Histopathological examination of the specimen confirmed a pathological Complete Response (pCR). This case supports the feasibility and potential efficacy of combining preoperative immunotherapy with surgery in the management of advanced PM.

Nivolumab in pretreated pleural mesothelioma: Results from an observational real-world study of patients treated within the AIFA 5% Fund.

BACKGROUND: Pleural mesothelioma is a rare cancer with a dismal prognosis and few therapeutic options, especially in the pretreated setting. Immunotherapy with checkpoint inhibitors as single agents yielded interesting results in refractory pleural mesothelioma, achieving a response rate between 10-20%, median progression-free survival of 2-5 months and median overall survival of 7-13 months. PATIENTS AND METHODS: A retrospective, multi-institutional study of pleural mesothelioma patients treated with nivolumab in second and further line was performed. The endpoints of the study are response rate, disease control rate, progression free survival and overall survival. RESULTS: Sixty-five patients with pleural mesothelioma treated with nivolumab in second and further line were enrolled at seven Italian institutions. The response rate was 8%, disease control rate was 37%, median progression free survival was 5.7 months (95% CI: 2.9-9.0) and median overall survival was 11.1 (95% CI 6.2-19.9) months. A higher neutrophils and neutrophils to lymphocytes ratio at baseline were associated with worse prognosis. CONCLUSION: Nivolumab as a single agent is fairly active in a cohort of unselected pretreated pleural mesothelioma patients. Further investigations on clinical and translational factors are needed to define which patient might benefit most from nivolumab treatment in pleural mesothelioma.

Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.

Mesothelioma comprises a group of rare cancers arising from the mesothelium of the pleura, peritoneum, tunica vaginalis testis and pericardium. Mesothelioma is generally associated with asbestos exposure and has a dismal prognosis, with few therapeutic options. Several next generation sequencing (NGS) experiments have been performed on mesothelioma arising at different sites. These studies highlight a genomic landscape mainly characterized by a high prevalence (>20%) of genomic aberrations leading to functional losses in oncosuppressor genes such as BAP1, CDKN2A, NF2, SETD2 and TP53. Nevertheless, to date, evidence of the effect of targeting these alterations with specific drugs is lacking. Conversely, 1-2% of mesothelioma might harbor activating mutations in oncogenes with specifically approved drugs. The goal of this review is to summarize NGS applications in mesothelioma and to provide insights into target therapy of mesothelioma guided by NGS.