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Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients
BACKGROUND & AIMS: Immunotherapy represents the new standard of care in systemic first-line treatment of hepatocellular carcinoma (HCC). Biomarkers that predict treatment response and survival remain an unmet clinical need. METHODS: Patients with HCC treated with immune-checkpoint inhibitors (IC...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081755/ https://www.ncbi.nlm.nih.gov/pubmed/37027398 http://dx.doi.org/10.1371/journal.pone.0282680 |
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author | Balcar, Lorenz Bauer, David Pomej, Katharina Meischl, Tobias Mandorfer, Mattias Reiberger, Thomas Trauner, Michael Scheiner, Bernhard Pinter, Matthias |
author_facet | Balcar, Lorenz Bauer, David Pomej, Katharina Meischl, Tobias Mandorfer, Mattias Reiberger, Thomas Trauner, Michael Scheiner, Bernhard Pinter, Matthias |
author_sort | Balcar, Lorenz |
collection | PubMed |
description | BACKGROUND & AIMS: Immunotherapy represents the new standard of care in systemic first-line treatment of hepatocellular carcinoma (HCC). Biomarkers that predict treatment response and survival remain an unmet clinical need. METHODS: Patients with HCC treated with immune-checkpoint inhibitors (ICI) between 10/2017 and 03/2022 were retrospectively evaluated. Immunoglobulin levels (IgG, IgM, IgA) were measured at baseline and six weeks after initiation of ICI treatment. Impact of relative changes on overall survival (OS), progression-free survival (PFS), and time to progression (TTP) were evaluated. RESULTS: Seventy-two patients with HCC receiving ICI (mostly atezolizumab/bevacizumab n = 54,75%) were included (mean age: 68±12 years, cirrhosis: 72%, mean Child-Turcotte-Pugh [CTP] score: 7±2 points). Most patients had a preserved performance status (ECOG-PS 0, n = 45, 63%), 25 (35%) showed macrovascular invasion, and 32 (44%) had extrahepatic spread. Baseline immunoglobulin values (median, IgG: 1395mg/dL, IgM: 337mg/dL, IgA: 89mg/dL) were not different between responders and non-responders, and neither baseline nor follow-up immunoglobulin values correlated with OS, PFS, and TTP. However, the relative change in IgG (Δ-IgG) independently predicted OS in multivariable Cox regression analysis after adjusting for severity of liver disease, baseline AFP and CRP as well as for Δ-IgA and Δ-IgM. Patients could be stratified into high (Δ-IgG≥+14%) vs. low (Δ-IgG<+14%) risk groups (median OS: 6.4 vs. 15.9 months; p = 0.001). Importantly, Δ-IgG was also associated with PFS and TTP on adjusted multivariable Cox regression analyses. CONCLUSION: Our study proposes a higher increase of Δ-IgG upon ICI treatment as a negative prognostic marker in patients with HCC, independent of underlying liver disease severity. These results require independent validation. |
format | Online Article Text |
id | pubmed-10081755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-100817552023-04-08 Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients Balcar, Lorenz Bauer, David Pomej, Katharina Meischl, Tobias Mandorfer, Mattias Reiberger, Thomas Trauner, Michael Scheiner, Bernhard Pinter, Matthias PLoS One Research Article BACKGROUND & AIMS: Immunotherapy represents the new standard of care in systemic first-line treatment of hepatocellular carcinoma (HCC). Biomarkers that predict treatment response and survival remain an unmet clinical need. METHODS: Patients with HCC treated with immune-checkpoint inhibitors (ICI) between 10/2017 and 03/2022 were retrospectively evaluated. Immunoglobulin levels (IgG, IgM, IgA) were measured at baseline and six weeks after initiation of ICI treatment. Impact of relative changes on overall survival (OS), progression-free survival (PFS), and time to progression (TTP) were evaluated. RESULTS: Seventy-two patients with HCC receiving ICI (mostly atezolizumab/bevacizumab n = 54,75%) were included (mean age: 68±12 years, cirrhosis: 72%, mean Child-Turcotte-Pugh [CTP] score: 7±2 points). Most patients had a preserved performance status (ECOG-PS 0, n = 45, 63%), 25 (35%) showed macrovascular invasion, and 32 (44%) had extrahepatic spread. Baseline immunoglobulin values (median, IgG: 1395mg/dL, IgM: 337mg/dL, IgA: 89mg/dL) were not different between responders and non-responders, and neither baseline nor follow-up immunoglobulin values correlated with OS, PFS, and TTP. However, the relative change in IgG (Δ-IgG) independently predicted OS in multivariable Cox regression analysis after adjusting for severity of liver disease, baseline AFP and CRP as well as for Δ-IgA and Δ-IgM. Patients could be stratified into high (Δ-IgG≥+14%) vs. low (Δ-IgG<+14%) risk groups (median OS: 6.4 vs. 15.9 months; p = 0.001). Importantly, Δ-IgG was also associated with PFS and TTP on adjusted multivariable Cox regression analyses. CONCLUSION: Our study proposes a higher increase of Δ-IgG upon ICI treatment as a negative prognostic marker in patients with HCC, independent of underlying liver disease severity. These results require independent validation. Public Library of Science 2023-04-07 /pmc/articles/PMC10081755/ /pubmed/37027398 http://dx.doi.org/10.1371/journal.pone.0282680 Text en © 2023 Balcar et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Balcar, Lorenz Bauer, David Pomej, Katharina Meischl, Tobias Mandorfer, Mattias Reiberger, Thomas Trauner, Michael Scheiner, Bernhard Pinter, Matthias Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
title | Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
title_full | Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
title_fullStr | Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
title_full_unstemmed | Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
title_short | Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
title_sort | early changes in immunoglobulin g levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081755/ https://www.ncbi.nlm.nih.gov/pubmed/37027398 http://dx.doi.org/10.1371/journal.pone.0282680 |
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