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Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report

BACKGROUND: Distinguishing pseudo-progression from true progression on immunotherapy remains a clinical challenge. Clinical tools to aid in this task are currently lacking. DNA mismatch repair (MMR) status is a known predictive marker for anti-programmed death (PD)-1 therapy, but its role in helping...

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Autores principales: Zhu, Mojun, Ganesan, Chitra, Flanagan, Siobhan, Yoon, Harry H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007936/
https://www.ncbi.nlm.nih.gov/pubmed/36915442
http://dx.doi.org/10.21037/jgo-22-709
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author Zhu, Mojun
Ganesan, Chitra
Flanagan, Siobhan
Yoon, Harry H.
author_facet Zhu, Mojun
Ganesan, Chitra
Flanagan, Siobhan
Yoon, Harry H.
author_sort Zhu, Mojun
collection PubMed
description BACKGROUND: Distinguishing pseudo-progression from true progression on immunotherapy remains a clinical challenge. Clinical tools to aid in this task are currently lacking. DNA mismatch repair (MMR) status is a known predictive marker for anti-programmed death (PD)-1 therapy, but its role in helping to address this situation is not well-defined. CASE DESCRIPTION: We report the first case, to our knowledge, of life-threatening hyper-progression which was later revealed to be pseudo-progression in a patient with a deficient MMR (dMMR) tumor. We describe a 62-year-old man with advanced dMMR gastric cancer who was being treated with pembrolizumab monotherapy. After three doses of pembrolizumab he exhibited signs and symptoms that met all applicable definitions of hyper-progression in the setting of acute life-threatening gastrointestinal hemorrhage, extensive radiographic progression of metastases, and increasing carcinoembryonic antigen (CEA). Comfort measures were considered given the appearance of hyper-progression. But partly given the patient’s request, aggressive support was provided, including blood products, vasopressors, and splenic artery embolization. His condition improved, and subsequent scans revealed regression of his metastases and decreased CEA, confirming pseudo-progression. Pembrolizumab was restarted. The patient remains on pembrolizumab with minimal tumor burden more than one year later. CONCLUSIONS: This case demonstrates that life-threatening hyper-progression can represent pseudo-progression and suggests that MMR status could be important to consider in determining the aggressiveness of clinical management during apparent hyper-progression.
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spelling pubmed-100079362023-03-12 Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report Zhu, Mojun Ganesan, Chitra Flanagan, Siobhan Yoon, Harry H. J Gastrointest Oncol Case Report BACKGROUND: Distinguishing pseudo-progression from true progression on immunotherapy remains a clinical challenge. Clinical tools to aid in this task are currently lacking. DNA mismatch repair (MMR) status is a known predictive marker for anti-programmed death (PD)-1 therapy, but its role in helping to address this situation is not well-defined. CASE DESCRIPTION: We report the first case, to our knowledge, of life-threatening hyper-progression which was later revealed to be pseudo-progression in a patient with a deficient MMR (dMMR) tumor. We describe a 62-year-old man with advanced dMMR gastric cancer who was being treated with pembrolizumab monotherapy. After three doses of pembrolizumab he exhibited signs and symptoms that met all applicable definitions of hyper-progression in the setting of acute life-threatening gastrointestinal hemorrhage, extensive radiographic progression of metastases, and increasing carcinoembryonic antigen (CEA). Comfort measures were considered given the appearance of hyper-progression. But partly given the patient’s request, aggressive support was provided, including blood products, vasopressors, and splenic artery embolization. His condition improved, and subsequent scans revealed regression of his metastases and decreased CEA, confirming pseudo-progression. Pembrolizumab was restarted. The patient remains on pembrolizumab with minimal tumor burden more than one year later. CONCLUSIONS: This case demonstrates that life-threatening hyper-progression can represent pseudo-progression and suggests that MMR status could be important to consider in determining the aggressiveness of clinical management during apparent hyper-progression. AME Publishing Company 2023-02-14 2023-02-28 /pmc/articles/PMC10007936/ /pubmed/36915442 http://dx.doi.org/10.21037/jgo-22-709 Text en 2023 Journal of Gastrointestinal Oncology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Case Report
Zhu, Mojun
Ganesan, Chitra
Flanagan, Siobhan
Yoon, Harry H.
Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report
title Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report
title_full Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report
title_fullStr Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report
title_full_unstemmed Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report
title_short Life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in DNA mismatch repair deficiency: a case report
title_sort life-threatening “hyper-progression” on immunotherapy revealed as pseudo-progression in dna mismatch repair deficiency: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007936/
https://www.ncbi.nlm.nih.gov/pubmed/36915442
http://dx.doi.org/10.21037/jgo-22-709
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