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Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

2020; BMJ; Volume: 8; Issue: 1 Linguagem: Inglês

10.1136/jitc-2020-000713

2051-1426

Anna Minchom, Wei Yuan, Mateus Crespo, Bora Gürel, Ines Figueiredo, Andrew Wotherspoon, Susana Miranda, Ruth Riisnaes, Ana Ferreira, Cláudia Bertan, Rita Pereira, Matt Clarke, Chloe Baker, Joo Ern Ang, Nicos Fotiadis, Nina Tunariu, Suzanne Carreira, Sanjay Popat, Mary O’Brien, Udai Banerji, Johann S. de Bono, Juanita Lopez,

Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis

Background This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. Case presentation A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1. Conclusion This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights.