{
  "abstract": "Introduction\n\nImmune-related adverse events (irAEs) frequently occur during combination immune checkpoint inhibition. However, their prognostic impact may vary according to organ involvement and severity. In this study, we exploratorily evaluated whether severe non-endocrine irAEs represent a temporally distinct and prognostically unfavorable clinical phenotype in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab.Patients and methods\n\nWe analyzed 63 patients with mRCC treated with ipilimumab plus nivolumab who were followed for at least 5 years. Patients were categorized into non-irAE, non-severe + severe endocrine irAE, and severe non-endocrine irAE groups. Overall survival (OS) was assessed. Multistate modeling was used to evaluate the transitions between treatment, irAE occurrence, and death. Landmark analyses were performed at 8 and 12 weeks to address immortal time bias.Results\n\nThe severe non-endocrine irAE group was associated with inferior OS. The multistate analysis revealed a potentially increased risk of direct transition from ipilimumab plus nivolumab to death in the severe non-endocrine irAE group. A significantly higher proportion of patients in the severe non-endocrine irAE group experienced irAEs within 30 days. No significant association was observed in the 8- and 12-week landmark analyses.Conclusion\n\nIn this exploratory retrospective study, severe non-endocrine irAEs showed an association with early onset and potentially unfavorable clinical outcomes in patients with mRCC receiving ipilimumab plus nivolumab. Given the limited sample size, these findings should be interpreted cautiously and require confirmation in larger independent cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.",
    "Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.",
    "Department of Urology, Kainan Hospital, Yatomi, Aichi, Japan.",
    "Department of Urology, Anjo Kosei Hospital, Anjo, Aichi, Japan.",
    "Department of Urology, Toyota Kosei Hospital, Toyota, Aichi, Japan.",
    "Department of Urology, Konan Kosei Hospital, Konan, Aichi, Japan.",
    "Department of Urology, Nagoya Tokushukai General Hospital, Kasugai, Aichi, Japan.",
    "Department of Urology, Gamagori City General Hospital, Gamagori, Aichi, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yoshihiko Tasaki",
      "orcid": "0000-0002-1830-7452"
    },
    {
      "affs": [
        0
      ],
      "name": "Kazumasa Sato"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuzo Hamamoto",
      "orcid": "0000-0002-9968-7468"
    },
    {
      "affs": [
        0
      ],
      "name": "Yosuke Sugiyama",
      "orcid": "0000-0001-8436-5872"
    },
    {
      "affs": [
        1
      ],
      "name": "Hiroaki Ikoma"
    },
    {
      "affs": [
        1
      ],
      "name": "Kengo Kawase",
      "orcid": "0000-0003-4176-9089"
    },
    {
      "affs": [
        2
      ],
      "name": "Hiroko Suzuki"
    },
    {
      "affs": [
        3
      ],
      "name": "Yusuke Noda"
    },
    {
      "affs": [
        4
      ],
      "name": "Masayuki Usami",
      "orcid": "0000-0003-0389-5682"
    },
    {
      "affs": [
        5
      ],
      "name": "Yohei Tsubouchi"
    },
    {
      "affs": [
        6
      ],
      "name": "Ryuga Kato"
    },
    {
      "affs": [
        7
      ],
      "name": "Takuya Sakata",
      "orcid": "0009-0006-6125-6626"
    },
    {
      "affs": [
        0
      ],
      "name": "Misato Tomita"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshihisa Mimura",
      "orcid": "0000-0001-5337-6835"
    },
    {
      "affs": [
        1
      ],
      "name": "Takashi Nagai",
      "orcid": "0000-0002-9635-4553"
    },
    {
      "affs": [
        1
      ],
      "name": "Rei Unno",
      "orcid": "0000-0003-0584-3712"
    },
    {
      "affs": [
        1
      ],
      "name": "Toshiki Etani"
    },
    {
      "affs": [
        1
      ],
      "name": "Taku Naiki",
      "orcid": "0000-0002-7638-6048"
    },
    {
      "affs": [
        1
      ],
      "name": "Takahiro Yasui",
      "orcid": "0000-0003-2197-2477"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoko Furukawa-Hibi",
      "orcid": "0000-0002-2126-5652"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dsfjfm9h44eqa.bib",
  "cited_by": 0,
  "doi": "10.1002/cam4.72410",
  "fulltext_url": "https://europepmc.org/articles/PMC13680286",
  "id": "dsfjfm9h44eqa",
  "issns": [
    "2045-7634"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897107",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
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  "openalex": "W7222972462",
  "pdf_url": "https://europepmc.org/articles/PMC13680286?pdf=render",
  "pmcid": "PMC13680286",
  "pmid": "42897107",
  "published": "2026-10-01",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/dsfjfm9h44eqa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42897107",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897107"
    },
    {
      "first_seen": "2026-10-30T13:44:37Z",
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      "url": "https://doi.org/10.1002/cam4.72410"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
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  ],
  "title": "Impact of Organ-Specific Severe Immune-Related Adverse Events on Long-Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5-Year Multicenter Multistate Analysis.",
  "title_text": "Impact of Organ-Specific Severe Immune-Related Adverse Events on Long-Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5-Year Multicenter Multistate Analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:37Z",
  "url": "https://research.draconitic.com/paper/dsfjfm9h44eqa",
  "venue": "Cancer medicine",
  "versions": []
}