{"title":"免疫相关不良事件对低PD-L1表达的晚期非小细胞肺癌患者临床结局的影响，重点是肺炎：日本的一项多中心回顾性研究","authors":"Shiho Goda, Tadaaki Yamada, Kenji Morimoto, Tae Hata, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Asuka Okada, Makoto Hibino, Yusuke Chihara, Takashi Kijima, Koichi Takayama","doi":"10.21037/tlcr-2024-1177","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC.</p><p><strong>Methods: </strong>We retrospectively enrolled 850 patients with programmed cell death ligand-1 (PD-L1) 1-49% advanced NSCLC who were treated with chemotherapy alone or with combined immunotherapy and chemotherapy as first-line treatment at 19 different institutions in Japan between March 2017 and June 2022. Using data from their medical records, we examined the type and severity of irAEs and their association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS).</p><p><strong>Results: </strong>OS and PFS were not significantly different between patients with and without severe irAEs. However, in the group receiving combined immunotherapy and chemotherapy, those who developed pneumonitis within 42 days of treatment initiation had shorter OS and PFS, irrespective of the pneumonitis grade, and a worse prognosis than those who received chemotherapy alone. Additionally, early-onset pneumonitis was more likely in patients aged >75 years, those with high lactate dehydrogenase levels, and those receiving steroids or immunosuppressants, suggesting that these factors may contribute to the risk of early-onset pneumonitis.</p><p><strong>Conclusions: </strong>Early-onset pneumonitis is a poor prognostic factor in patients with PD-L1 1-49% advanced NSCLC receiving combined immunotherapy and chemotherapy. Further large-scale observational studies are warranted to confirm these findings.</p><p><strong>Keywords: </strong>Non-small cell lung cancer (NSCLC); severe immune-related adverse events (irAEs); pneumonitis.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":"14 4","pages":"1185-1196"},"PeriodicalIF":4.0000,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082213/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impact of immune-related adverse events on clinical outcomes in patients with advanced non-small cell lung cancer with low PD-L1 expression, focusing on pneumonitis: a multicenter retrospective study in Japan.\",\"authors\":\"Shiho Goda, Tadaaki Yamada, Kenji Morimoto, Tae Hata, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Asuka Okada, Makoto Hibino, Yusuke Chihara, Takashi Kijima, Koichi Takayama\",\"doi\":\"10.21037/tlcr-2024-1177\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC.</p><p><strong>Methods: </strong>We retrospectively enrolled 850 patients with programmed cell death ligand-1 (PD-L1) 1-49% advanced NSCLC who were treated with chemotherapy alone or with combined immunotherapy and chemotherapy as first-line treatment at 19 different institutions in Japan between March 2017 and June 2022. Using data from their medical records, we examined the type and severity of irAEs and their association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS).</p><p><strong>Results: </strong>OS and PFS were not significantly different between patients with and without severe irAEs. However, in the group receiving combined immunotherapy and chemotherapy, those who developed pneumonitis within 42 days of treatment initiation had shorter OS and PFS, irrespective of the pneumonitis grade, and a worse prognosis than those who received chemotherapy alone. Additionally, early-onset pneumonitis was more likely in patients aged >75 years, those with high lactate dehydrogenase levels, and those receiving steroids or immunosuppressants, suggesting that these factors may contribute to the risk of early-onset pneumonitis.</p><p><strong>Conclusions: </strong>Early-onset pneumonitis is a poor prognostic factor in patients with PD-L1 1-49% advanced NSCLC receiving combined immunotherapy and chemotherapy. Further large-scale observational studies are warranted to confirm these findings.</p><p><strong>Keywords: </strong>Non-small cell lung cancer (NSCLC); severe immune-related adverse events (irAEs); pneumonitis.</p>\",\"PeriodicalId\":23271,\"journal\":{\"name\":\"Translational lung cancer research\",\"volume\":\"14 4\",\"pages\":\"1185-1196\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-04-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082213/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational lung cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tlcr-2024-1177\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational lung cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tlcr-2024-1177","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Impact of immune-related adverse events on clinical outcomes in patients with advanced non-small cell lung cancer with low PD-L1 expression, focusing on pneumonitis: a multicenter retrospective study in Japan.
Background: Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC.
Methods: We retrospectively enrolled 850 patients with programmed cell death ligand-1 (PD-L1) 1-49% advanced NSCLC who were treated with chemotherapy alone or with combined immunotherapy and chemotherapy as first-line treatment at 19 different institutions in Japan between March 2017 and June 2022. Using data from their medical records, we examined the type and severity of irAEs and their association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS).
Results: OS and PFS were not significantly different between patients with and without severe irAEs. However, in the group receiving combined immunotherapy and chemotherapy, those who developed pneumonitis within 42 days of treatment initiation had shorter OS and PFS, irrespective of the pneumonitis grade, and a worse prognosis than those who received chemotherapy alone. Additionally, early-onset pneumonitis was more likely in patients aged >75 years, those with high lactate dehydrogenase levels, and those receiving steroids or immunosuppressants, suggesting that these factors may contribute to the risk of early-onset pneumonitis.
Conclusions: Early-onset pneumonitis is a poor prognostic factor in patients with PD-L1 1-49% advanced NSCLC receiving combined immunotherapy and chemotherapy. Further large-scale observational studies are warranted to confirm these findings.
Keywords: Non-small cell lung cancer (NSCLC); severe immune-related adverse events (irAEs); pneumonitis.
期刊介绍：
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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