{"entity":{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","aka":["immune-related adverse event"],"tldr":"Immune-related adverse events (irAEs) are the autoimmune side effects of checkpoint inhibitors: colitis, thyroid problems, rash, hepatitis, pneumonitis.","summary":"Immune-related adverse events (irAEs) are the autoimmune side effects of Immune checkpoint inhibitors, including colitis, thyroid problems, rash, hepatitis and pneumonitis. Any organ can be affected, and they are most frequent and most severe when CTLA-4 and PD-1 blockade are combined. Management relies on steroids and biologics; some irAEs, notably the endocrinopathies, are permanent, and their occurrence correlates only weakly with response. The term is cited by the Melanoma and Mesothelioma entries and the drug records for Toripalimab, Tislelizumab and Camrelizumab, by the bottlenecks on toxicity and on predicting immunotherapy response, and by ideas on testing drugs in old and unhealthy animals and reading the immune response in blood three weeks in.","asOf":"2026-09-04","links":[{"label":"Haanen et al., Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline (Annals of Oncology 2022)","url":"https://doi.org/10.1016/j.annonc.2022.10.001"},{"label":"Macmillan: pembrolizumab","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"},{"label":"Breast Cancer Now: pembrolizumab (Keytruda)","url":"https://breastcancernow.org/about-breast-cancer/treatment/targeted-therapy/pembrolizumab-keytruda"},{"label":"Schneider et al., ASCO guideline on immune-related adverse events (JCO 2021)","url":"https://doi.org/10.1200/JCO.21.01440"},{"label":"Macmillan: pembrolizumab (Keytruda)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/pembrolizumab"},{"label":"Macmillan: durvalumab (Imfinzi)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/durvalumab"},{"label":"Macmillan: atezolizumab (Tecentriq)","url":"https://www.macmillan.org.uk/cancer-information-and-support/treatments-and-drugs/atezolizumab"}],"tags":[],"related":[],"cancers":["tnbc","lung-cancer","nsclc","sclc"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-haanen-ann-oncol"],"journals":[],"dependsOn":[],"notes":["Pembrolizumab before and after surgery for triple-negative breast cancer: Macmillan says the treatment can make the immune system too active, that side effects can start during treatment or after it ends, and that glands making hormones (such as the thyroid) can be permanently affected, sometimes needing daily tablets. Breast Cancer Now says you should be given an alert card listing the symptoms to report and an out-of-hours contact.","The symptoms both charities ask you to report straight away on the 24-hour number: more stools than usual, stools at night, watery stools or tummy cramps (bowel inflammation); breathlessness, a cough that does not go away, wheeze or fever (lung inflammation); yellow skin or eyes, sickness (liver inflammation); unusual tiredness, headaches that do not go away, dizziness, thirst or passing more urine (hormone glands).","Lung cancer: checkpoint treatment is used at every stage of lung cancer, so the same warning list applies whether it is given before surgery, after chemoradiotherapy or for cancer that has spread. Macmillan says to contact the hospital straight away on the 24-hour number for breathlessness, a cough that does not go away, wheezing or a fever over 37.5 C (lung inflammation); for passing more stools than is normal for you or passing stools at night (bowel inflammation); for a spreading rash, blistering or peeling skin with flu-like symptoms; and for a temperature above 37.5 C or below 36 C or feeling unwell with a normal temperature. It also says these can start during treatment or after treatment ends, which is why the patient alert card is worth carrying."],"category":"Side effects","wikipediaChecked":"2026-09-22"},"route":"/terms/irae/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"cutaneous-scc","kind":"cancer","name":"Cutaneous squamous cell carcinoma","route":"/cancers/cutaneous-scc/"},{"id":"kaposi-sarcoma","kind":"cancer","name":"Kaposi sarcoma","route":"/cancers/kaposi-sarcoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"merkel-cell-carcinoma","kind":"cancer","name":"Merkel cell carcinoma","route":"/cancers/merkel-cell-carcinoma/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"thymic-carcinoma","kind":"cancer","name":"Thymic carcinoma","route":"/cancers/thymic-carcinoma/"},{"id":"thymoma","kind":"cancer","name":"Thymoma (WHO types A, AB, B1, B2 and B3)","route":"/cancers/thymoma/"},{"id":"thymic-epithelial","kind":"cancer","name":"Thymoma and thymic carcinoma","route":"/cancers/thymic-epithelial/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"rejuv-recovery-endocrine-permanence","kind":"technology","name":"Immune endocrine damage is usually permanent, and almost nobody is told","route":"/technologies/rejuv-recovery-endocrine-permanence/"},{"id":"cardiac-biomarker-monitoring","kind":"technology","name":"Troponin and natriuretic peptide monitoring during cancer treatment","route":"/technologies/cardiac-biomarker-monitoring/"}],"paper":[{"id":"paper-asco-irae-guideline-jco-2021","kind":"paper","name":"ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors","route":"/key-papers/paper-asco-irae-guideline-jco-2021/"},{"id":"paper-checkmate-067-10-year-nejm-2025","kind":"paper","name":"CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma","route":"/key-papers/paper-checkmate-067-10-year-nejm-2025/"},{"id":"paper-hodi-ipilimumab-melanoma-nejm-2010","kind":"paper","name":"Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma","route":"/key-papers/paper-hodi-ipilimumab-melanoma-nejm-2010/"},{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/"},{"id":"paper-keynote-522-nejm-2022","kind":"paper","name":"KEYNOTE-522: adding pembrolizumab before and after surgery in early triple-negative breast cancer","route":"/key-papers/paper-keynote-522-nejm-2022/"},{"id":"paper-keynote-564-nejm-2021","kind":"paper","name":"KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery","route":"/key-papers/paper-keynote-564-nejm-2021/"},{"id":"paper-haanen-ann-oncol","kind":"paper","name":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","route":"/key-papers/paper-haanen-ann-oncol/"},{"id":"paper-nadina-nejm-2024","kind":"paper","name":"NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma","route":"/key-papers/paper-nadina-nejm-2024/"},{"id":"paper-niche-2-nejm-2024","kind":"paper","name":"NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients","route":"/key-papers/paper-niche-2-nejm-2024/"},{"id":"paper-pacific-nejm-2017","kind":"paper","name":"PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer","route":"/key-papers/paper-pacific-nejm-2017/"},{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/"},{"id":"paper-relativity-047-nejm-2022","kind":"paper","name":"RELATIVITY-047: relatlimab plus nivolumab, the first LAG-3 checkpoint combination, in untreated advanced melanoma","route":"/key-papers/paper-relativity-047-nejm-2022/"},{"id":"paper-ribas-wolchok-checkpoint-blockade-science-2018","kind":"paper","name":"Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade","route":"/key-papers/paper-ribas-wolchok-checkpoint-blockade-science-2018/"},{"id":"paper-swog-s1826-nivolumab-avd-nejm-2024","kind":"paper","name":"SWOG S1826: nivolumab plus AVD chemotherapy versus brentuximab-AVD for advanced Hodgkin lymphoma in adolescents and adults","route":"/key-papers/paper-swog-s1826-nivolumab-avd-nejm-2024/"},{"id":"paper-topalian-anti-pd1-nejm-2012","kind":"paper","name":"Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer","route":"/key-papers/paper-topalian-anti-pd1-nejm-2012/"}],"drug":[{"id":"camrelizumab","kind":"drug","name":"Camrelizumab","route":"/drugs/camrelizumab/"},{"id":"tislelizumab","kind":"drug","name":"Tislelizumab","route":"/drugs/tislelizumab/"},{"id":"toripalimab","kind":"drug","name":"Toripalimab","route":"/drugs/toripalimab/"}],"term":[{"id":"carers-breast-cancer-uk","kind":"term","name":"Carers: what you can do and UK carer support (breast cancer)","route":"/terms/carers-breast-cancer-uk/"},{"id":"ctcae-grading","kind":"term","name":"CTCAE toxicity grading (grade 3-4 adverse events)","route":"/terms/ctcae-grading/"},{"id":"gvhd","kind":"term","name":"Graft-versus-host disease (GVHD) and graft-versus-leukaemia","route":"/terms/gvhd/"},{"id":"hepatotoxicity","kind":"term","name":"Hepatotoxicity (liver enzyme elevation)","route":"/terms/hepatotoxicity/"},{"id":"immune-checkpoint","kind":"term","name":"Immune checkpoint","route":"/terms/immune-checkpoint/"},{"id":"immune-colitis","kind":"term","name":"Immune-mediated colitis and diarrhoea","route":"/terms/immune-colitis/"},{"id":"immune-endocrinopathy","kind":"term","name":"Immune-related endocrinopathies (thyroiditis, hypophysitis)","route":"/terms/immune-endocrinopathy/"},{"id":"myocarditis","kind":"term","name":"Immune-related myocarditis","route":"/terms/myocarditis/"},{"id":"immuno-oncology","kind":"term","name":"Immuno-oncology (IO) and checkpoint blockade","route":"/terms/immuno-oncology/"},{"id":"immunotherapy-term","kind":"term","name":"Immunotherapy","route":"/terms/immunotherapy-term/"},{"id":"pneumonitis","kind":"term","name":"Pneumonitis","route":"/terms/pneumonitis/"},{"id":"rash-skin-toxicity","kind":"term","name":"Rash and skin toxicity (acneiform rash, paronychia)","route":"/terms/rash-skin-toxicity/"},{"id":"side-effect-vs-adverse-event","kind":"term","name":"Side effect versus adverse event","route":"/terms/side-effect-vs-adverse-event/"},{"id":"skin-cancer-after-organ-transplant","kind":"term","name":"Skin cancer after an organ transplant","route":"/terms/skin-cancer-after-organ-transplant/"},{"id":"toxicity-grade","kind":"term","name":"Toxicity grade","route":"/terms/toxicity-grade/"},{"id":"urgent-help-tnbc","kind":"term","name":"When to seek urgent help with triple-negative breast cancer (NHS 111 and 999)","route":"/terms/urgent-help-tnbc/"},{"id":"hedgehog-inhibitor-tolerability","kind":"term","name":"Why people stop taking hedgehog inhibitors","route":"/terms/hedgehog-inhibitor-tolerability/"}],"trial":[{"id":"admec-o","kind":"trial","name":"ADMEC-O (adjuvant nivolumab in completely resected Merkel cell carcinoma)","route":"/trials/admec-o/"},{"id":"c-post","kind":"trial","name":"C-POST (cemiplimab after surgery and radiotherapy for high-risk skin squamous cell carcinoma)","route":"/trials/c-post/"},{"id":"cemiplimab-kidney-transplant-cscc","kind":"trial","name":"Cemiplimab for kidney transplant recipients with advanced skin squamous cell carcinoma","route":"/trials/cemiplimab-kidney-transplant-cscc/"},{"id":"cemiplimab-advanced-bcc","kind":"trial","name":"Cemiplimab in basal cell carcinoma after a hedgehog inhibitor","route":"/trials/cemiplimab-advanced-bcc/"},{"id":"gepardouze","kind":"trial","name":"GeparDouze / NSABP B-59","route":"/trials/gepardouze/"},{"id":"javelin-merkel-200","kind":"trial","name":"JAVELIN Merkel 200","route":"/trials/javelin-merkel-200/"},{"id":"keynote-017","kind":"trial","name":"KEYNOTE-017 (Cancer Immunotherapy Trials Network 09)","route":"/trials/keynote-017/"},{"id":"neoadjuvant-cemiplimab-cscc","kind":"trial","name":"Neoadjuvant cemiplimab for resectable stage II to IV skin squamous cell carcinoma","route":"/trials/neoadjuvant-cemiplimab-cscc/"},{"id":"pod1um-201","kind":"trial","name":"POD1UM-201 (retifanlimab in advanced Merkel cell carcinoma)","route":"/trials/pod1um-201/"}],"bottleneck":[{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","route":"/bottlenecks/b-cachexia-supportive/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"idea":[{"id":"idea-tr1-tolerability-estimands","kind":"idea","name":"Define tolerability endpoints as rigorously as efficacy endpoints","route":"/ideas/idea-tr1-tolerability-estimands/"},{"id":"idea-tr1-post-marketing-safety-by-ancestry-and-sex","kind":"idea","name":"Post-marketing safety monitoring stratified by ancestry and sex, with label updates","route":"/ideas/idea-tr1-post-marketing-safety-by-ancestry-and-sex/"},{"id":"idea-moon-irae-prediction-and-prevention","kind":"idea","name":"Predict immune side-effects before they happen and pre-empt them","route":"/ideas/idea-moon-irae-prediction-and-prevention/"},{"id":"idea-bio1-aged-comorbid-models","kind":"idea","name":"Test cancer drugs in old and unhealthy animals, not just young fit ones","route":"/ideas/idea-bio1-aged-comorbid-models/"},{"id":"idea-moon-toxicity-first-endpoints","kind":"idea","name":"Tolerability as a co-primary endpoint with its own label claim","route":"/ideas/idea-moon-toxicity-first-endpoints/"},{"id":"idea-data-toxicity-cds-for-nurses","kind":"idea","name":"Toxicity-management decision support for nurses and pharmacists","route":"/ideas/idea-data-toxicity-cds-for-nurses/"},{"id":"idea-bio2-steroid-sparing-irae","kind":"idea","name":"Treat immunotherapy side-effects without wiping out the response","route":"/ideas/idea-bio2-steroid-sparing-irae/"},{"id":"idea-bio2-lymph-node-immune-priming","kind":"idea","name":"Treat the draining lymph node before removing it","route":"/ideas/idea-bio2-lymph-node-immune-priming/"},{"id":"idea-bio2-tcr-repertoire-early-readout","kind":"idea","name":"Watch the immune system's response in the blood three weeks in","route":"/ideas/idea-bio2-tcr-repertoire-early-readout/"},{"id":"idea-tr1-win-ratio-net-benefit-endpoint","kind":"idea","name":"Win-ratio endpoints that weigh survival, toxicity and quality of life together","route":"/ideas/idea-tr1-win-ratio-net-benefit-endpoint/"}],"journal":[{"id":"jitc","kind":"journal","name":"Journal for ImmunoTherapy of Cancer","route":"/journals/jitc/"}],"institution":[{"id":"mascc","kind":"institution","name":"Multinational Association of Supportive Care in Cancer","route":"/institutions/mascc/"},{"id":"sitc","kind":"institution","name":"Society for Immunotherapy of Cancer","route":"/institutions/sitc/"},{"id":"vanderbilt-ingram","kind":"institution","name":"Vanderbilt-Ingram Cancer Center","route":"/institutions/vanderbilt-ingram/"}],"pathway":[{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"}]}}