Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers
Purpose The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH. Methods All patients treated with ICIs between September 2014 and April 2019 at our institution...
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| Veröffentlicht in: | Journal of cancer research and clinical oncology 2021-06, Vol.147 (6), p.1747-1756 |
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| creator | Yamamoto, Atsushi Yano, Yoshihiko Ueda, Yoshihide Yasutomi, Eiichiro Hatazawa, Yuri Hayashi, Hiroki Yoshida, Ryutaro Asaji, Naoki Shiomi, Yuuki Tobimatsu, Kazutoshi Sakai, Arata Kodama, Yuzo |
| description | Purpose
The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH.
Methods
All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined.
Results
Overall, 250 patients (median age 71 years; range 30–87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5–38.0;
P
= 0.0002) and ipilimumab–nivolumab combination therapy (OR 61.2; 95% CI 7.9–1275.3;
P
|
| doi_str_mv | 10.1007/s00432-020-03448-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2518562468</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2518562468</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-e0b58671a3df47665893a136dc6dca1575d3fd65b12ac362e17ff2dffa8ebdff3</originalsourceid><addsrcrecordid>eNp9kEtLxDAUhYMozjj6B1xIwHU0jyatSxl8geBG1yFNE5txmtYkReffm7Gj7oTAzb33nHPhA-CU4AuCcXkZMS4YRZhihFlRVKjaA3OyHRHG-D6YY1ISxCkRM3AU4wrnnpf0EMwYo5RiwucgLdfOO63W0BqVxmAi7C10XTd6gzrTOJVMA1szqNSn_tNplzbQ-WbUeVxvdkqoW6Pfht75lJetq13qQ8xfmH3O-BThh0st1MprE-IxOLBqHc3Jri7Ay-3N8_IePT7dPSyvH5FmJU_I4JpXoiSKNbYoheDVFVOEiUbnpwgvecNsI3hNqNJMUENKa2ljrapMnQtbgPMpdwj9-2hikqt-DD6flJSTigtaiCqr6KTSoY8xGCuH4DoVNpJguQUtJ9Ayg5bfoOXWdLaLHuuM6dfyQzYL2CSIeeVfTfi7_U_sFxHNi7g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2518562468</pqid></control><display><type>article</type><title>Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers</title><source>SpringerLink Journals - AutoHoldings</source><creator>Yamamoto, Atsushi ; Yano, Yoshihiko ; Ueda, Yoshihide ; Yasutomi, Eiichiro ; Hatazawa, Yuri ; Hayashi, Hiroki ; Yoshida, Ryutaro ; Asaji, Naoki ; Shiomi, Yuuki ; Tobimatsu, Kazutoshi ; Sakai, Arata ; Kodama, Yuzo</creator><creatorcontrib>Yamamoto, Atsushi ; Yano, Yoshihiko ; Ueda, Yoshihide ; Yasutomi, Eiichiro ; Hatazawa, Yuri ; Hayashi, Hiroki ; Yoshida, Ryutaro ; Asaji, Naoki ; Shiomi, Yuuki ; Tobimatsu, Kazutoshi ; Sakai, Arata ; Kodama, Yuzo</creatorcontrib><description>Purpose
The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH.
Methods
All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined.
Results
Overall, 250 patients (median age 71 years; range 30–87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5–38.0;
P
= 0.0002) and ipilimumab–nivolumab combination therapy (OR 61.2; 95% CI 7.9–1275.3;
P
< 0.0001).
Conclusion
Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient’s prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab–nivolumab combination therapy.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-020-03448-8</identifier><identifier>PMID: 33222015</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Cancer Research ; Hematology ; Hepatotoxicity ; Immune checkpoint ; Internal Medicine ; Medical records ; Medicine ; Medicine & Public Health ; Melanoma ; Oncology ; Original Article – Clinical Oncology ; Patients ; Risk factors ; Skin cancer ; Steroid hormones ; Therapeutic applications ; Transaminase</subject><ispartof>Journal of cancer research and clinical oncology, 2021-06, Vol.147 (6), p.1747-1756</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-e0b58671a3df47665893a136dc6dca1575d3fd65b12ac362e17ff2dffa8ebdff3</citedby><cites>FETCH-LOGICAL-c375t-e0b58671a3df47665893a136dc6dca1575d3fd65b12ac362e17ff2dffa8ebdff3</cites><orcidid>0000-0002-5177-7480</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-020-03448-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-020-03448-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33222015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamamoto, Atsushi</creatorcontrib><creatorcontrib>Yano, Yoshihiko</creatorcontrib><creatorcontrib>Ueda, Yoshihide</creatorcontrib><creatorcontrib>Yasutomi, Eiichiro</creatorcontrib><creatorcontrib>Hatazawa, Yuri</creatorcontrib><creatorcontrib>Hayashi, Hiroki</creatorcontrib><creatorcontrib>Yoshida, Ryutaro</creatorcontrib><creatorcontrib>Asaji, Naoki</creatorcontrib><creatorcontrib>Shiomi, Yuuki</creatorcontrib><creatorcontrib>Tobimatsu, Kazutoshi</creatorcontrib><creatorcontrib>Sakai, Arata</creatorcontrib><creatorcontrib>Kodama, Yuzo</creatorcontrib><title>Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Purpose
The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH.
Methods
All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined.
Results
Overall, 250 patients (median age 71 years; range 30–87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5–38.0;
P
= 0.0002) and ipilimumab–nivolumab combination therapy (OR 61.2; 95% CI 7.9–1275.3;
P
< 0.0001).
Conclusion
Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient’s prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab–nivolumab combination therapy.</description><subject>Cancer Research</subject><subject>Hematology</subject><subject>Hepatotoxicity</subject><subject>Immune checkpoint</subject><subject>Internal Medicine</subject><subject>Medical records</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Melanoma</subject><subject>Oncology</subject><subject>Original Article – Clinical Oncology</subject><subject>Patients</subject><subject>Risk factors</subject><subject>Skin cancer</subject><subject>Steroid hormones</subject><subject>Therapeutic applications</subject><subject>Transaminase</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kEtLxDAUhYMozjj6B1xIwHU0jyatSxl8geBG1yFNE5txmtYkReffm7Gj7oTAzb33nHPhA-CU4AuCcXkZMS4YRZhihFlRVKjaA3OyHRHG-D6YY1ISxCkRM3AU4wrnnpf0EMwYo5RiwucgLdfOO63W0BqVxmAi7C10XTd6gzrTOJVMA1szqNSn_tNplzbQ-WbUeVxvdkqoW6Pfht75lJetq13qQ8xfmH3O-BThh0st1MprE-IxOLBqHc3Jri7Ay-3N8_IePT7dPSyvH5FmJU_I4JpXoiSKNbYoheDVFVOEiUbnpwgvecNsI3hNqNJMUENKa2ljrapMnQtbgPMpdwj9-2hikqt-DD6flJSTigtaiCqr6KTSoY8xGCuH4DoVNpJguQUtJ9Ayg5bfoOXWdLaLHuuM6dfyQzYL2CSIeeVfTfi7_U_sFxHNi7g</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Yamamoto, Atsushi</creator><creator>Yano, Yoshihiko</creator><creator>Ueda, Yoshihide</creator><creator>Yasutomi, Eiichiro</creator><creator>Hatazawa, Yuri</creator><creator>Hayashi, Hiroki</creator><creator>Yoshida, Ryutaro</creator><creator>Asaji, Naoki</creator><creator>Shiomi, Yuuki</creator><creator>Tobimatsu, Kazutoshi</creator><creator>Sakai, Arata</creator><creator>Kodama, Yuzo</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-5177-7480</orcidid></search><sort><creationdate>20210601</creationdate><title>Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers</title><author>Yamamoto, Atsushi ; Yano, Yoshihiko ; Ueda, Yoshihide ; Yasutomi, Eiichiro ; Hatazawa, Yuri ; Hayashi, Hiroki ; Yoshida, Ryutaro ; Asaji, Naoki ; Shiomi, Yuuki ; Tobimatsu, Kazutoshi ; Sakai, Arata ; Kodama, Yuzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-e0b58671a3df47665893a136dc6dca1575d3fd65b12ac362e17ff2dffa8ebdff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cancer Research</topic><topic>Hematology</topic><topic>Hepatotoxicity</topic><topic>Immune checkpoint</topic><topic>Internal Medicine</topic><topic>Medical records</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Melanoma</topic><topic>Oncology</topic><topic>Original Article – Clinical Oncology</topic><topic>Patients</topic><topic>Risk factors</topic><topic>Skin cancer</topic><topic>Steroid hormones</topic><topic>Therapeutic applications</topic><topic>Transaminase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamamoto, Atsushi</creatorcontrib><creatorcontrib>Yano, Yoshihiko</creatorcontrib><creatorcontrib>Ueda, Yoshihide</creatorcontrib><creatorcontrib>Yasutomi, Eiichiro</creatorcontrib><creatorcontrib>Hatazawa, Yuri</creatorcontrib><creatorcontrib>Hayashi, Hiroki</creatorcontrib><creatorcontrib>Yoshida, Ryutaro</creatorcontrib><creatorcontrib>Asaji, Naoki</creatorcontrib><creatorcontrib>Shiomi, Yuuki</creatorcontrib><creatorcontrib>Tobimatsu, Kazutoshi</creatorcontrib><creatorcontrib>Sakai, Arata</creatorcontrib><creatorcontrib>Kodama, Yuzo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamamoto, Atsushi</au><au>Yano, Yoshihiko</au><au>Ueda, Yoshihide</au><au>Yasutomi, Eiichiro</au><au>Hatazawa, Yuri</au><au>Hayashi, Hiroki</au><au>Yoshida, Ryutaro</au><au>Asaji, Naoki</au><au>Shiomi, Yuuki</au><au>Tobimatsu, Kazutoshi</au><au>Sakai, Arata</au><au>Kodama, Yuzo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>147</volume><issue>6</issue><spage>1747</spage><epage>1756</epage><pages>1747-1756</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Purpose
The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH.
Methods
All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined.
Results
Overall, 250 patients (median age 71 years; range 30–87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5–38.0;
P
= 0.0002) and ipilimumab–nivolumab combination therapy (OR 61.2; 95% CI 7.9–1275.3;
P
< 0.0001).
Conclusion
Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient’s prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab–nivolumab combination therapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33222015</pmid><doi>10.1007/s00432-020-03448-8</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5177-7480</orcidid></addata></record> |
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| subjects | Cancer Research Hematology Hepatotoxicity Immune checkpoint Internal Medicine Medical records Medicine Medicine & Public Health Melanoma Oncology Original Article – Clinical Oncology Patients Risk factors Skin cancer Steroid hormones Therapeutic applications Transaminase |
| title | Clinical features of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in patients with cancers |
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