Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody

Abstract Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the a...

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Autores principales:	Takeshi Azuma, Takumi Takeuchi, Yukihide Matayoshi, Shin Namiki, Tetsuya Obara, Kazuhiro Imamura, Mikio Takamori
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2a6f8c097636447083d21605efcde241
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spelling	oai:doaj.org-article:2a6f8c097636447083d21605efcde2412021-12-02T16:50:17ZSerum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody10.1038/s41598-021-88744-02045-2322https://doaj.org/article/2a6f8c097636447083d21605efcde2412021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88744-0https://doaj.org/toc/2045-2322Abstract Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.Takeshi AzumaTakumi TakeuchiYukihide MatayoshiShin NamikiTetsuya ObaraKazuhiro ImamuraMikio TakamoriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takeshi Azuma Takumi Takeuchi Yukihide Matayoshi Shin Namiki Tetsuya Obara Kazuhiro Imamura Mikio Takamori Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
description	Abstract Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.
format	article
author	Takeshi Azuma Takumi Takeuchi Yukihide Matayoshi Shin Namiki Tetsuya Obara Kazuhiro Imamura Mikio Takamori
author_facet	Takeshi Azuma Takumi Takeuchi Yukihide Matayoshi Shin Namiki Tetsuya Obara Kazuhiro Imamura Mikio Takamori
author_sort	Takeshi Azuma
title	Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
title_short	Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
title_full	Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
title_fullStr	Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
title_full_unstemmed	Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody
title_sort	serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-pd-1 or anti-ctla-4 antibody
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2a6f8c097636447083d21605efcde241
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Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody

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