{"entity":{"id":"irae-pneumonitis","kind":"protocol","name":"Immune-related pneumonitis from checkpoint inhibitors, by grade","aka":["checkpoint inhibitor pneumonitis","CIP","immune checkpoint inhibitor lung inflammation","ICI pneumonitis management","immunotherapy pneumonitis"],"tldr":"Immunotherapy can inflame the lungs. A new cough, breathlessness or chest pain during or after immunotherapy should be reported to your cancer team the same day. A CT scan of the chest confirms it, and steroids are the main treatment; severe cases need hospital and steroids through a drip.","summary":"Pneumonitis occurs in about 4% of people on PD-(L)1 inhibitors (1% grade 3 or more), 1% on anti-CTLA-4 and 7% on combinations in trials, with higher rates in single-centre practice (19% in one series) and in lung and kidney cancer, smokers, people with asthma or prior chest radiotherapy (SITC 2021). Median onset is about 3 months.\n\nSITC 2021: high-resolution CT of the chest for suspected pneumonitis, with pulmonary function tests (spirometry and DLCO) if the CT is negative. Grade 2: prednisone 1 to 2 mg/kg/day, tapered over 4 to 6 weeks. Grade 3 or more: intravenous methylprednisolone 1 to 2 mg/kg/day, tapered over 4 to 6 weeks. If high-dose steroids do not help within 72 hours, or the illness is life-threatening, the options, in no order, are mycophenolate mofetil, high-dose IVIG, infliximab, cyclophosphamide or tocilizumab, each on low-level evidence. After grade 2, re-challenge may follow complete resolution, with closer follow-up; recurrence was 25% in a small series.\n\nASCO 2021 gives the general frame: hold for grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, permanently stop for grade 4. The Chinese 2022 consensus grades by symptoms and the share of lung involved on CT, monitors grade 1, treats grades 2 to 3 with prednisolone-equivalent 1 to 2 mg/kg/day, assesses response at 48 to 72 hours and keeps steroid courses to 6 to 8 weeks, not over 12. ESMO 2022 could not be read.","asOf":"2026-11-11","links":[],"tags":["protocol","irae","acute-oncology"],"related":["irae-colitis","idea-bio2-steroid-sparing-irae"],"cancers":[],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["pembrolizumab","nivolumab","ipilimumab","atezolizumab","durvalumab","cemiplimab","dostarlimab","tremelimumab","avelumab","prednisone","cyclophosphamide","tocilizumab","methylprednisolone"],"companies":[],"institutions":["sitc","asco","esmo"],"pathways":[],"terms":["pneumonitis","irae"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-asco-irae-guideline-jco-2021"],"journals":[],"dependsOn":[],"notes":[],"simple":"Immunotherapy can sometimes inflame the lungs. If you become breathless or start coughing, ring your cancer helpline. Steroids usually help.","domain":"immunotherapy-toxicity","setting":{"who":["patient-or-carer","nurse","doctor","pharmacist"],"where":["telephone-triage","acute-oncology-service","outpatient-clinic","emergency-department","ward","intensive-care"]},"population":"Adults treated with an immune checkpoint inhibitor, alone or combined, who develop new or worsening breathlessness, cough, chest pain, fever or low oxygen, or new changes on a chest scan. Radiation pneumonitis and infection are differential diagnoses, not covered here. Children are not addressed.","trigger":"New or worsening cough, breathlessness, chest pain or falling oxygen saturation during or after checkpoint inhibitor treatment, or new lung changes on a routine scan.","steps":[{"action":"Before starting, refer people with existing autoimmune interstitial lung disease to a lung specialist for lung function tests and risk assessment","why":"Existing lung scarring raises the risk of pneumonitis, so a baseline helps both the decision to treat and later comparison.","source":"sitc-2021","quote":"Patients with pre-existing autoimmune ILD should be referred to a specialist where possible before initiation of ICI therapy for the consideration of pulmonary function tests (PFTs) and risk assessment","grade":"LE: 3"},{"action":"Teach the patient that a new cough, breathlessness or chest pain must be reported promptly","why":"Pneumonitis can worsen quickly, so it needs prompt assessment.","source":"sitc-2021","quote":"Patients should receive dedicated education on irAEs by a medical professional and may receive additional materials such as informational booklets or reference cards."},{"action":"Arrange a high-resolution CT of the chest for suspected pneumonitis; if it is normal, consider lung function tests including spirometry and DLCO","why":"CT shows the inflammation; lung function tests can find a deficit that the scan misses.","source":"sitc-2021","quote":"Patients with suspected pneumonitis should be examined via high-resolution CT of the chest. If the CT scan is negative, PFTs should be considered to identify a potential functional deficit","grade":"LE: 4"},{"action":"Look for infection and other causes alongside, without delaying treatment","why":"Infection, clots, heart failure, radiation pneumonitis and the cancer itself can all look like pneumonitis.","source":"sitc-2021","quote":"Diagnostic evaluation for all irAEs should attempt to rule out other possible etiologies (eg, diarrhea/colitis associated with Clostridium difficile infection), but treatment for irAEs should be initiated as is deemed clinically appropriate."},{"action":"For grade 1, keep monitoring; for grade 2, hold the checkpoint inhibitor","why":"Under the general rules, grade 1 can continue with close follow-up and grade 2 needs a pause and treatment.","source":"sitc-2021","quote":"Unless otherwise specified, patients experiencing grade 2 irAEs should have ICI therapy temporarily withheld and be treated with corticosteroids depending on the toxicity in question."},{"action":"For grade 2, give prednisone 1 to 2 mg/kg/day (or equivalent) and taper over 4 to 6 weeks; for grade 3 or more, give intravenous methylprednisolone 1 to 2 mg/kg/day and taper over 4 to 6 weeks","why":"Steroids settle the inflammation in most people; the slower taper reduces relapse.","source":"sitc-2021","quote":"Patients experiencing grade 2 pneumonitis should receive 1–2 mg/kg/day prednisone (or equivalent), tapering over 4–6 weeks. For pneumonitis of grade ≥3, patients should receive 1–2 mg/kg/day methylprednisolone IV or equivalent, tapering over 4–6 weeks","grade":"LE: 3"},{"action":"Counsel about steroid side effects, including Pneumocystis pneumonia","why":"Long courses of high-dose steroids raise the risk of infection, high blood sugar and mood change.","source":"sitc-2021","quote":"When beginning corticosteroid therapy, patients should be specifically counseled about potential toxicities, including hyperglycemia, mood disturbances, insomnia, gastritis, weight gain, and opportunistic infections (eg, Pneumocystis pneumonia)","grade":"LE: 1"},{"action":"For grade 3, suspend the checkpoint inhibitor; after grade 4, stop it permanently","why":"Life-threatening pneumonitis generally rules out further checkpoint inhibitor treatment under ASCO's general rules.","source":"asco-2021","quote":"In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, except for endocrinopathies that have been controlled by hormone replacement.","grade":"expert consensus"},{"action":"If there is no improvement within 72 hours of high-dose steroids, or the illness is life-threatening, add a second immunosuppressant with a lung specialist","why":"Steroid-refractory pneumonitis has a high death rate; SITC lists mycophenolate mofetil, high-dose IVIG, infliximab, cyclophosphamide or tocilizumab in no particular order.","source":"sitc-2021","quote":"If high-dose corticosteroid therapy does not improve pneumonitis symptoms within 72 hours (or if symptoms are life-threatening), options include (in no particular order) mycophenolate mofetil (1–1.5 g two times per day, tapering in consultation with a pulmonary specialist","grade":"LE: 3 (mycophenolate), LE: 4 (IVIG, infliximab, tocilizumab)"},{"action":"After grade 2 pneumonitis, consider re-challenge only once symptoms have fully resolved, with more frequent review afterwards","why":"Pneumonitis can come back, with or without re-challenge.","source":"sitc-2021","quote":"If patients have experienced grade 2 pneumonitis, they may be re-challenged with ICIs upon complete resolution of symptoms. These patients should be monitored through more frequent consultations with their physician","grade":"LE: 4"}],"bestInClass":{"statement":"SITC 2021 is the most detailed guideline that could be read: high-resolution chest CT, prednisone 1 to 2 mg/kg/day for grade 2 and intravenous methylprednisolone 1 to 2 mg/kg/day for grade 3 or more, each tapered over 4 to 6 weeks (LE: 3), a second immunosuppressant after 72 hours without response, and re-challenge after grade 2 only when symptoms have fully resolved. ASCO 2021 agrees on the frame and on a taper of at least 4 to 6 weeks, and permanently stops checkpoint inhibitors after grade 4. The Chinese 2022 consensus adds CT extent to the grade, a 48 to 72 hour response check and a 6 to 8 week, at most 12 week, steroid course. ESMO 2022 was not read. All the second-line drugs rest on case series or small cohorts; none has been compared in a randomised trial that could be read.","sources":["sitc-2021","asco-2021","cn-cip-2022","esmo-2022"]},"variants":[{"name":"Grading by CT extent and a fixed steroid course (Chinese expert consensus, 2022)","differs":"Grades pneumonitis by symptoms together with the share of lung involved on CT (under 25%, 25 to 50%, over 50%), recommends prednisolone-equivalent 1 to 2 mg/kg/day for grades 2 to 3 and intravenous steroids for more severe or acute cases, checks response at 48 to 72 hours and limits the course to 6 to 8 weeks, not more than 12. It judges Pneumocystis prophylaxis generally unnecessary except for 20 mg a day for more than 6 weeks.","evidence":"Expert consensus, not graded.","sources":["cn-cip-2022"]},{"name":"Permanent stop after grade 4 (ASCO 2021)","differs":"States permanent discontinuation for grade 4 toxicities in general; SITC allows re-challenge only after grade 2 pneumonitis.","evidence":"Expert consensus.","sources":["asco-2021"]}],"grades":[{"claim":"Grade 2: prednisone 1 to 2 mg/kg/day; grade 3 or more: intravenous methylprednisolone 1 to 2 mg/kg/day; taper over 4 to 6 weeks","grade":"LE: 3","source":"sitc-2021"},{"claim":"High-resolution chest CT for suspected pneumonitis; lung function tests if CT is negative","grade":"LE: 4","source":"sitc-2021"},{"claim":"Mycophenolate mofetil for steroid-refractory pneumonitis","grade":"LE: 3","source":"sitc-2021"},{"claim":"High-dose IVIG, infliximab or tocilizumab for steroid-refractory pneumonitis","grade":"LE: 4","source":"sitc-2021"},{"claim":"Re-challenge after grade 2 once symptoms have completely resolved","grade":"LE: 4","source":"sitc-2021"},{"claim":"Steroid taper over at least 4 to 6 weeks; permanent discontinuation after grade 4","grade":"expert consensus","source":"asco-2021","quote":"Corticosteroids should be tapered over the course of at least 4-6 weeks."},{"claim":"Response to steroids assessed within 48 to 72 hours","grade":"expert consensus (not graded)","source":"cn-cip-2022","quote":"For CIP, clinical improvements should be assessed within 48 to 72 hours of GCS treatment."}],"sources":[{"key":"sitc-2021","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2021,"url":"https://europepmc.org/article/PMC/PMC8237720","doi":"10.1136/jitc-2021-002435","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); a recommendation without an LE is expert consensus, approved by at least 75% of the voting panel.","read":"full-text","accessed":"2026-11-11"},{"key":"asco-2021","label":"Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update","publisher":"ASCO, Journal of Clinical Oncology","year":2021,"url":"https://europepmc.org/abstract/MED/34724392","doi":"10.1200/JCO.21.01440","gradingScheme":"The abstract states that, because high-quality evidence is scarce, the recommendations are based on expert consensus (informal consensus process).","read":"abstract","accessed":"2026-11-11"},{"key":"esmo-2022","label":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","publisher":"ESMO, Annals of Oncology","year":2022,"url":"https://doi.org/10.1016/j.annonc.2022.10.001","doi":"10.1016/j.annonc.2022.10.001","read":"not-reachable","accessed":"2026-11-11"},{"key":"cn-cip-2022","label":"Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor","publisher":"Thoracic Cancer (Chinese expert panel)","year":2022,"url":"https://europepmc.org/article/PMC/PMC9715776","doi":"10.1111/1759-7714.14693","gradingScheme":"Nine consensus statements; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["The ESMO 2022 guideline on toxicities from immunotherapy could not be read: Europe PMC holds no abstract and the publisher's page refused a script. Its grade-by-grade advice is not stated here and no step rests on it.","The ASCO 2021 guideline update was read only as its abstract, which gives the general rules (continue for grade 1, hold for most grade 2, high-dose steroids for grade 3, taper over at least 4 to 6 weeks, stop for grade 4) but not its organ-by-organ tables.","A 2025 Chinese expert consensus on the diagnosis and management of checkpoint inhibitor pneumonitis (doi 10.3760/cma.j.cn112147-20241121-00694) is listed in Europe PMC without open full text; it was not read.","SITC names an ECOG-ACRIN trial comparing IVIG with infliximab for steroid-refractory pneumonitis; its result was not looked for here, and no randomised evidence on second-line treatment was read.","Guidelines differ on whether steroid courses for pneumonitis need Pneumocystis prophylaxis; SITC asks for counselling, the Chinese consensus limits prophylaxis to 20 mg a day for more than 6 weeks, and the ASCO and ESMO positions were not read."]},"route":"/protocols/irae-pneumonitis/","neighbours":{"protocol":[{"id":"checkpoint-inhibitor-baseline-and-monitoring","kind":"protocol","name":"Baseline tests and monitoring before and during checkpoint inhibitor treatment","route":"/protocols/checkpoint-inhibitor-baseline-and-monitoring/"},{"id":"irae-hypophysitis-adrenal","kind":"protocol","name":"Checkpoint inhibitor hypophysitis and adrenal insufficiency: emergency treatment, replacement and steroid emergency card","route":"/protocols/irae-hypophysitis-adrenal/"},{"id":"irae-hepatitis","kind":"protocol","name":"Immune-mediated hepatitis from checkpoint inhibitors, by grade","route":"/protocols/irae-hepatitis/"},{"id":"irae-colitis","kind":"protocol","name":"Immune-related diarrhoea and colitis from checkpoint inhibitors, by grade","route":"/protocols/irae-colitis/"},{"id":"irae-rechallenge","kind":"protocol","name":"Restarting a checkpoint inhibitor after an immune-related side effect","route":"/protocols/irae-rechallenge/"},{"id":"irae-steroid-taper-and-pjp","kind":"protocol","name":"Steroid taper after immunotherapy side effects, with Pneumocystis prophylaxis and adrenal checks","route":"/protocols/irae-steroid-taper-and-pjp/"}],"idea":[{"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/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"atezolizumab","kind":"drug","name":"Atezolizumab","route":"/drugs/atezolizumab/"},{"id":"avelumab","kind":"drug","name":"Avelumab","route":"/drugs/avelumab/"},{"id":"cemiplimab","kind":"drug","name":"Cemiplimab","route":"/drugs/cemiplimab/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"dostarlimab","kind":"drug","name":"Dostarlimab","route":"/drugs/dostarlimab/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"methylprednisolone","kind":"drug","name":"Methylprednisolone","route":"/drugs/methylprednisolone/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"tocilizumab","kind":"drug","name":"Tocilizumab","route":"/drugs/tocilizumab/"},{"id":"tremelimumab","kind":"drug","name":"Tremelimumab","route":"/drugs/tremelimumab/"}],"institution":[{"id":"asco","kind":"institution","name":"American Society of Clinical Oncology (ASCO)","route":"/institutions/asco/"},{"id":"esmo","kind":"institution","name":"European Society for Medical Oncology (ESMO)","route":"/institutions/esmo/"},{"id":"sitc","kind":"institution","name":"Society for Immunotherapy of Cancer","route":"/institutions/sitc/"}],"term":[{"id":"irae","kind":"term","name":"Immune-related adverse events (irAEs)","route":"/terms/irae/"},{"id":"pneumonitis","kind":"term","name":"Pneumonitis","route":"/terms/pneumonitis/"}],"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/"}]}}