{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:37:05Z","timestamp":1793191025865,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King\u2019s College London"},{"name":"Oxford Hospitals Charity"},{"name":"the limbic"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Purpose: Evaluation of predictors and outcomes in NSCLC patients treated with an immune checkpoint inhibitor (ICI) following a severe immune-related adverse event (irAE). Methods: We included all NSCLC patients receiving \u22651 ICI cycle and corticosteroids for CTCAE Grade \u22653 irAEs between 2017 and 2023 from three UK NHS teaching hospitals. Progression-free survival (PFS) and overall survival (OS) after the 1st irAE, best overall response (BOR) to ICI, and predictors of clinical benefit were evaluated. Kaplan\u2013Meier, Cox and logistic regression models, and Wilcoxon tests were used. Results: We screened 1658 NSCLC patients and identified 80 eligible subjects. The majority of patients had metastatic (n = 50, 63%) vs. localized (n = 30, 37%) NSCLC. Most patients developed a single \u2265Grade 3 irAE on 1st line ICI (n = 71, 89%). Overall, 14 (18%) patients developed 2nd irAEs, 7 after rechallenge with ICIs. In the complete cohort, median OS after 1st irAE was 15.84 months (95% CI, 12.45\u201326.91). Lower neutrophil-to-lymphocyte ratio (NLR), patients receiving &gt;4 cycles of ICI or median duration of ICI of &gt;2.76 months before 1st irAE were associated with improved OS (p &lt; 0.05), the latter two with PFS (p &lt; 0.05). Age, gender, stage, KRAS mutation, PD-L1 and ICI type were not associated with PFS or OS. Pneumonitis as 1st irAE had the worst PFS and OS (p &lt; 0.05). Median starting corticosteroid dose of \u226460 mg for 1st irAE had an improved OS (p = 0.04). Post 1st irAE response associated with better PFS and OS (p &lt; 0.05). Number and duration of irAEs and additional immunosuppressive agents (14% of patients) were not associated with PFS or OS. Conclusions: In \u2265Grade 3 irAEs patients managed with corticosteroids, lower baseline NLR, longer ICI use, response to ICI after 1st irAE, and a \u226460 mg corticosteroid dose had promising outcomes.<\/jats:p>","DOI":"10.3390\/cancers17172819","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T15:03:14Z","timestamp":1756393394000},"page":"2819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Predictors and Outcomes of Non-Small Cell Lung Carcinoma Patients Following Severe Immune Checkpoint Inhibitor Toxicity: A Real-World UK Multi-Centre Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Umair","family":"Mahmood","sequence":"first","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, UK"},{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"},{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Josephides","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"},{"name":"Guy\u2019s Hospital, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenali","family":"Chitnis","sequence":"additional","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Skwarski","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5635-7696","authenticated-orcid":false,"given":"Spyridon","family":"Gennatas","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmistha","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Spicer","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"},{"name":"Guy\u2019s Hospital, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Karapanagiotou","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"},{"name":"Guy\u2019s Hospital, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Forster","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Jamal-Hanjani","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"},{"name":"Cancer Metastasis Laboratory, University College London Cancer Institute, London WC1E 6DD, UK"},{"name":"Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London WC1E 6DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Benafif","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Swanton","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"},{"name":"Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London WC1E 6DD, UK"},{"name":"Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siow-Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dionysis","family":"Papadatos-Pastos","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London NW1 2PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-9251","authenticated-orcid":false,"given":"Alexandros","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 3SS, UK"},{"name":"Guy\u2019s Hospital, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Coupe","sequence":"additional","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","article-title":"Fundamental mechanisms of immune checkpoint blockade therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature14292","article-title":"Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer","volume":"520","author":"Rech","year":"2015","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liu, S.Z., Jin, S.Z., Liu, X.D., and Sun, Y.M. 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