Recent advancements in immune checkpoint inhibitors (ICIs) underscore the importance of effectively managing immune-related adverse events (irAEs). This study aimed to systematically monitor the real-world occurrence of irAEs and assess their prognostic implications, including the influence of subsequent steroid therapy.
We retrospectively analyzed 1008 cancer patients treated with ICIs between 2014 and 2021, gathering comprehensive irAE data spanning their onset, management, and clinical outcomes. Of these patients, 458 (45.4%) experienced a total of 670 irAEs. Skin toxicity emerged as the most prevalent, followed by pneumonitis, hypothyroidism, hepatitis, adrenal insufficiency, and colitis.
Univariate Kaplan-Meier analysis showed that patients developing irAEs exhibited significantly prolonged overall survival (OS) compared to those who did not (22.1 months vs. 13.2 months, p < 0.0001). Patients administered steroids at a dosage of <2 mg/kg showed comparable prognoses to those without steroid treatment. However, individuals undergoing steroid pulse therapy, particularly for severe pneumonitis and hepatitis, displayed shorter OS (7.8 months vs. 23.4 months, p = 0.016). Moreover, steroid pulse therapy emerged as an adverse prognostic factor in multivariate analysis (hazard ratio: 2.19, 95% confidence interval: 1.34–2.86, p < 0.001).
In conclusion, prompt steroid intervention for irAEs does not compromise prognosis and should be promptly initiated to mitigate toxicity. Nevertheless, pulse therapy for severe cases constitutes a negative prognostic indicator, emphasizing the importance of early detection in managing such irAEs.
"},{"@language":"ja","@value":"免疫チェックポイント阻害薬(immune checkpoint inhibitor: ICI)の有害事象である免疫関連有害事象(immune-related adverse events: irAEs)は、ときに重篤化し患者の生命を危険に晒すため、その早期発見から治療までのマネジメントが重要である。本研究では、実臨床下におけるirAEの発生状況を調査し、irAEの発生およびその後のステロイド治療が患者の生命予後に与える影響について評価した。
2014年から2021年の間にICI治療を受けた1008名の患者を後方視的に調査し、irAEの発生、対応、臨床転帰にわたる包括的なデータを収集した。458名(45.4%)が670件のirEAを発症し、皮膚障害が最も多く、次いで間質性肺炎、甲状腺機能低下、肝炎、副腎不全、大腸炎であった。単変量Kaplan-Meier解析によると、irAEを発症した患者は発症しなかった患者に比べて全生存期間（OS）が有意に延長した（22.1ヶ月対13.2ヶ月、p<0.0001）。irAE発生後にステロイドを2mg/kg以下で投与された患者は、ステロイドを投与されなかった患者と同等の予後を示した。しかし、重症肺炎や肝障害に対しステロイドパルス療法を受けた患者は有意にOSが短かった（7.8ヶ月対23.4ヶ月、p=0.016）。さらに、ステロイドパルス療法の施行は多変量解析においても独立した予後不良因子として抽出された（ハザード比：2.19、95％信頼区間：1.34-2.86、p<0.001）。
結論として、irAEに対する2mg/kg以下のステロイド治療は患者予後に影響はなく、臓器毒性を軽減するため速やかに開始すべきである。一方で、一部の重症irAEに対するステロイドパルス療法は予後不良因子であり、この結果は重篤なirAEをより早期に発見し治療介入するためirAEマネジメントを構築する必要性を示唆している。
"}],"abstractLicenseFlag":"disallow"}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1410301319807531779","@type":"Researcher","foaf:name":[{"@language":"en","@value":"MATSUKANE Ryosuke"},{"@language":"ja","@value":"松金 良祐"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Kyushu University Hospital, Department of Pharmacy"},{"@language":"ja","@value":"九州大学病院 薬剤部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410301319807531776","@type":"Researcher","foaf:name":[{"@language":"en","@value":"SUETSUGU Kimitaka"},{"@language":"ja","@value":"末次 王卓"}],"jpcoar:affiliationName":[{"@language":"ja","@value":"九州大学病院 薬剤部"},{"@language":"en","@value":"Kyushu University Hospital, Department of Pharmacy"}]},{"@id":"https://cir.nii.ac.jp/crid/1410301319807531780","@type":"Researcher","foaf:name":[{"@language":"en","@value":"HIROTA Takeshi"},{"@language":"ja","@value":"廣田 豪"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Kyushu University Hospital, Department of Pharmacy"},{"@language":"ja","@value":"九州大学病院 薬剤部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410301319807531777","@type":"Researcher","foaf:name":[{"@language":"en","@value":"MINAMI Haruna"},{"@language":"ja","@value":"南 晴奈"}],"jpcoar:affiliationName":[{"@language":"en","@value":"Kyushu University Hospital, Department of Pharmacy"},{"@language":"ja","@value":"九州大学病院 薬剤部"}]},{"@id":"https://cir.nii.ac.jp/crid/1410301319807531778","@type":"Researcher","foaf:name":[{"@language":"en","@value":"IEIRI Ichiro"},{"@language":"ja","@value":"家入 一郎"}],"jpcoar:affiliationName":[{"@language":"ja","@value":"九州大学病院 薬剤部"},{"@language":"en","@value":"Kyushu University Hospital, Department of Pharmacy"}]}],"publication":{"prism:publicationName":[{"@language":"en","@value":"Annual Meeting of the Japanese Society of Toxicology"},{"@language":"ja","@value":"日本毒性学会学術年会"}],"dc:publisher":[{"@language":"en","@value":"The Japanese Society of Toxicology"},{"@language":"ja","@value":"日本毒性学会"}],"prism:publicationDate":"2024","prism:volume":"51.1","prism:number":"0","prism:startingPage":"P-96E"},"jpcoar:conferenceName":"第51回日本毒性学会学術年会","availableAt":"2024","dataSourceIdentifier":[{"@type":"JALC","@value":"oai:japanlinkcenter.org:2013337694"}]}