Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients.
<h4>Background & aims</h4>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.<h4>Methods</h4>Patients with HCC treated...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0282680 |
| _version_ | 1797847247198617600 |
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| author | Lorenz Balcar David Bauer Katharina Pomej Tobias Meischl Mattias Mandorfer Thomas Reiberger Michael Trauner Bernhard Scheiner Matthias Pinter |
| author_facet | Lorenz Balcar David Bauer Katharina Pomej Tobias Meischl Mattias Mandorfer Thomas Reiberger Michael Trauner Bernhard Scheiner Matthias Pinter |
| author_sort | Lorenz Balcar |
| collection | DOAJ |
| description | <h4>Background & aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| first_indexed | 2024-04-09T18:08:14Z |
| format | Article |
| id | doaj.art-c1f6db95759649faa460d130a0d02aad |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T18:08:14Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c1f6db95759649faa460d130a0d02aad2023-04-14T05:31:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01184e028268010.1371/journal.pone.0282680Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients.Lorenz BalcarDavid BauerKatharina PomejTobias MeischlMattias MandorferThomas ReibergerMichael TraunerBernhard ScheinerMatthias Pinter<h4>Background & aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0282680 |
| spellingShingle | Lorenz Balcar David Bauer Katharina Pomej Tobias Meischl Mattias Mandorfer Thomas Reiberger Michael Trauner Bernhard Scheiner Matthias Pinter Early changes in immunoglobulin G levels during immune checkpoint inhibitor treatment are associated with survival in hepatocellular carcinoma patients. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0282680 |
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