Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab
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 re...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000713.full |
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| author | Johann De Bono Nicos Fotiadis Sanjay Popat Anna Minchom Wei Yuan Mateus Crespo Bora Gurel Ines Figueiredo Andrew Wotherspoon Susana Miranda Ruth Riisnaes Ana Ferreira Claudia Bertan Rita Pereira Matt Clarke Chloe Baker Joo Ern Ang Nina Tunariu Suzanne Carreira Mary O'Brien Udai Banerji Juanita Lopez |
| author_facet | Johann De Bono Nicos Fotiadis Sanjay Popat Anna Minchom Wei Yuan Mateus Crespo Bora Gurel Ines Figueiredo Andrew Wotherspoon Susana Miranda Ruth Riisnaes Ana Ferreira Claudia Bertan Rita Pereira Matt Clarke Chloe Baker Joo Ern Ang Nina Tunariu Suzanne Carreira Mary O'Brien Udai Banerji Juanita Lopez |
| author_sort | Johann De Bono |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7e62949f48524365b46f3e0bf7017a58 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-7e62949f48524365b46f3e0bf7017a582024-11-09T10:10:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2020-000713Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumabJohann De Bono0Nicos Fotiadis1Sanjay Popat2Anna Minchom3Wei Yuan4Mateus Crespo5Bora Gurel6Ines Figueiredo7Andrew Wotherspoon8Susana Miranda9Ruth Riisnaes10Ana Ferreira11Claudia Bertan12Rita Pereira13Matt Clarke14Chloe Baker15Joo Ern Ang16Nina Tunariu17Suzanne Carreira18Mary O'Brien19Udai Banerji20Juanita Lopez21Institute of Cancer Research, London SM2 5NG, UK3 Department of Radiology, Royal Marsden Hospital, London, UK5 Lung Unit, Royal Marsden Hospital NHS Trust, London, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UKThe Institute of Cancer Research, London, UKThe Institute of Cancer Research, London, UKThe Institute of Cancer Research, London, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UKDepartment of Histopathology, Royal Marsden NHS Foundation Trust, London, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UKThe Institute of Cancer Research, London, UKCentro Hospitalar de Vila Nova de Gaia Espinho EPE, Vila Nova de Gaia, Porto, Portugal1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK1 Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UKThe Institute of Cancer Research, London, UK8 Department of Oncology, Royal Marsden Hospital NHS Trust, London, UKInstitute of Cancer Research, London, UKInstitute of Cancer Research, Royal Marsden Hospital, London, UKBackground 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.https://jitc.bmj.com/content/8/1/e000713.full |
| spellingShingle | Johann De Bono Nicos Fotiadis Sanjay Popat Anna Minchom Wei Yuan Mateus Crespo Bora Gurel Ines Figueiredo Andrew Wotherspoon Susana Miranda Ruth Riisnaes Ana Ferreira Claudia Bertan Rita Pereira Matt Clarke Chloe Baker Joo Ern Ang Nina Tunariu Suzanne Carreira Mary O'Brien Udai Banerji Juanita Lopez Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab Journal for ImmunoTherapy of Cancer |
| title | Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab |
| title_full | Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab |
| title_fullStr | Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab |
| title_full_unstemmed | Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab |
| title_short | Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab |
| title_sort | molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab |
| url | https://jitc.bmj.com/content/8/1/e000713.full |
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