Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.
Date
2020-03-01ICR Author
Author
Minchom, A
Yuan, W
Crespo, M
Gurel, B
Figueiredo, I
Wotherspoon, A
Miranda, S
Riisnaes, R
Ferreira, A
Bertan, C
Pereira, R
Clarke, M
Baker, C
Ang, JE
Fotiadis, N
Tunariu, N
Carreira, S
Popat, S
O'Brien, M
Banerji, U
de Bono, J
Lopez, J
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Mesothelioma
Lung Neoplasms
Pleural Neoplasms
Prognosis
Retreatment
Aged
Female
Antibodies, Monoclonal, Humanized
Biomarkers, Tumor
B7-H1 Antigen
Mesothelioma, Malignant
Research team
Medicine (de Bono Prostate)
Cancer Biomarkers
Clinical Pharmacology – Adaptive Therapy
Prostate Cancer Targeted Therapy Group
Thoracic Oncology
Treatment of thoracic tumours
Language
eng
Date accepted
2020-02-05
License start date
2020-03
Citation
Journal for immunotherapy of cancer, 2020, 8 (1)
Publisher
BMJ PUBLISHING GROUP