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Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab

CONTEXT: Metastatic adrenocortical carcinoma (ACC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. A subset of ACC is due to Lynch syndrome, an inherited tumor syndrome resulting from germline mutations in mismatch repair (MMR) genes. It has been demonstrated that...

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Autores principales: Casey, R.T., Giger, O., Seetho, I., Marker, A., Pitfield, D., Boyle, L.H., Gurnell, M., Shaw, A., Tischkowitz, M., Maher, E.R., Chatterjee, V.K., Janowitz, T., Mells, G., Corrie, P., Challis, B.G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: W.B. Saunders 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286406/
https://www.ncbi.nlm.nih.gov/pubmed/30262398
http://dx.doi.org/10.1053/j.seminoncol.2018.06.001
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author Casey, R.T.
Giger, O.
Seetho, I.
Marker, A.
Pitfield, D.
Boyle, L.H.
Gurnell, M.
Shaw, A.
Tischkowitz, M.
Maher, E.R.
Chatterjee, V.K.
Janowitz, T.
Mells, G.
Corrie, P.
Challis, B.G.
author_facet Casey, R.T.
Giger, O.
Seetho, I.
Marker, A.
Pitfield, D.
Boyle, L.H.
Gurnell, M.
Shaw, A.
Tischkowitz, M.
Maher, E.R.
Chatterjee, V.K.
Janowitz, T.
Mells, G.
Corrie, P.
Challis, B.G.
author_sort Casey, R.T.
collection PubMed
description CONTEXT: Metastatic adrenocortical carcinoma (ACC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. A subset of ACC is due to Lynch syndrome, an inherited tumor syndrome resulting from germline mutations in mismatch repair (MMR) genes. It has been demonstrated that several cancers characterized by MMR deficiency are sensitive to immune checkpoint inhibitors that target PD-1. Here, we provide the first report of PD-1 blockade with pembrolizumab in a patient with Lynch syndrome and progressive cortisol-secreting metastatic ACC. CASE REPORT: A 58-year-old female with known Lynch syndrome presented with severe Cushing's syndrome and was diagnosed with a cortisol-secreting ACC. Three months following surgical resection and adjuvant mitotane therapy the patient developed metastatic disease and persistent hypercortisolemia. She commenced pembrolizumab, but her second cycle was delayed due to a transient transaminitis. Computed tomography performed after 12 weeks and 2 cycles of pembrolizumab administration revealed significant disease progression and treatment was discontinued. After 7 weeks, the patient became jaundiced and soon died due to fulminant liver failure. CONCLUSION: Treatment of MMR-deficient cortisol-secreting ACC with pembrolizumab may be ineffective due to supraphysiological levels of circulating corticosteroids, which may in turn mask severe drug-induced organ damage.
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spelling pubmed-62864062018-12-17 Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab Casey, R.T. Giger, O. Seetho, I. Marker, A. Pitfield, D. Boyle, L.H. Gurnell, M. Shaw, A. Tischkowitz, M. Maher, E.R. Chatterjee, V.K. Janowitz, T. Mells, G. Corrie, P. Challis, B.G. Semin Oncol Article CONTEXT: Metastatic adrenocortical carcinoma (ACC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. A subset of ACC is due to Lynch syndrome, an inherited tumor syndrome resulting from germline mutations in mismatch repair (MMR) genes. It has been demonstrated that several cancers characterized by MMR deficiency are sensitive to immune checkpoint inhibitors that target PD-1. Here, we provide the first report of PD-1 blockade with pembrolizumab in a patient with Lynch syndrome and progressive cortisol-secreting metastatic ACC. CASE REPORT: A 58-year-old female with known Lynch syndrome presented with severe Cushing's syndrome and was diagnosed with a cortisol-secreting ACC. Three months following surgical resection and adjuvant mitotane therapy the patient developed metastatic disease and persistent hypercortisolemia. She commenced pembrolizumab, but her second cycle was delayed due to a transient transaminitis. Computed tomography performed after 12 weeks and 2 cycles of pembrolizumab administration revealed significant disease progression and treatment was discontinued. After 7 weeks, the patient became jaundiced and soon died due to fulminant liver failure. CONCLUSION: Treatment of MMR-deficient cortisol-secreting ACC with pembrolizumab may be ineffective due to supraphysiological levels of circulating corticosteroids, which may in turn mask severe drug-induced organ damage. W.B. Saunders 2018-06 /pmc/articles/PMC6286406/ /pubmed/30262398 http://dx.doi.org/10.1053/j.seminoncol.2018.06.001 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Casey, R.T.
Giger, O.
Seetho, I.
Marker, A.
Pitfield, D.
Boyle, L.H.
Gurnell, M.
Shaw, A.
Tischkowitz, M.
Maher, E.R.
Chatterjee, V.K.
Janowitz, T.
Mells, G.
Corrie, P.
Challis, B.G.
Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
title Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
title_full Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
title_fullStr Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
title_full_unstemmed Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
title_short Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
title_sort rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286406/
https://www.ncbi.nlm.nih.gov/pubmed/30262398
http://dx.doi.org/10.1053/j.seminoncol.2018.06.001
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