{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:50:44Z","timestamp":1785757844016,"version":"3.56.0"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":214,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Case Reports in Oncological Medicine"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Cyclin\u2010dependent kinase 4\/6 inhibitors (CDK4\/6i), when combined with endocrine therapy, have significantly transformed the management of hormone receptor\u2010positive, HER2\u2010negative metastatic breast cancer. Ribociclib, abemaciclib and palbociclib improve progression\u2010free survival and delay chemotherapy initiation, with ribociclib additionally demonstrating an overall survival advantage. The NATALEE trial has further expanded the role of CDK4\/6 inhibition in early breast cancer, showing significant improvement in 4\u2010year invasive disease\u2010free survival with adjuvant ribociclib in HR+\/HER2\u2010negative disease. Despite their shared mechanisms of targeting the CDK4\/6\u2013p16\u2013retinoblastoma pathway, these agents differ in pharmacokinetics, kinase selectivity and toxicity. Hepatoxicity is a recognised adverse event of ribociclib with all grade toxicity occurring in around 20% of patients and Grade 3\u20134 events in 11%\u201315%. This drug\u2010induced liver injury (DILI) typically resolves with drug withdrawal.Immune\u2010mediated or autoimmune\u2010like presentations of ribociclib\u2010associated hepatotoxicity have been reported, although detailed management strategies remain poorly described. We report a series of five patients who developed ribociclib\u2010induced liver injury that failed to improve with cessation of therapy, and instead demonstrated features suggestive of an immune\u2010mediated mechanism. Hepatotoxicity occurred predominantly within the first few treatment cycles, highlighting the importance of early monitoring. All patients experienced significant biochemical improvement with corticosteroids; however, three developed recurrent transaminase elevation during tapering. Two required tacrolimus as a steroid\u2010sparing agent, allowing eventual withdrawal of immunosuppression without relapse. Rechallenge with ribociclib in one patient led to recurrent hepatotoxicity, again responsive to steroids. Three patients were subsequently treated with palbociclib without recurrence of hepatotoxicity, maintaining disease control for more than 2 years. Liver biopsy in four patients was consistent with DILI in three and revealed mixed DILI with underlying primary biliary cholangitis in one, illustrating the complexity of managing hepatotoxicity in individuals with comorbid liver disease. This series highlights a pattern suggestive of immune\u2010mediated ribociclib\u2010induced hepatotoxicity responsive to short course corticosteroids with or without additional immunosuppression. Palbociclib appears to be a safe alternative, enabling continuation of CDK4\/6\u2013targeted therapy without premature transition to chemotherapy.<\/jats:p>","DOI":"10.1155\/crom\/2417755","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:41:53Z","timestamp":1785757313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune\u2010Mediated Hepatotoxicity Associated With Ribociclib: A Multipatient Case Series and Management Strategy"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6099-6772","authenticated-orcid":false,"given":"Jemma","family":"Buchalter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-0255","authenticated-orcid":false,"given":"Helen","family":"O\u2032Donovan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmet","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zita","family":"Galvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1938-8730","authenticated-orcid":false,"given":"Janice M.","family":"Walshe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.09.019"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/GO.23.00411"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2114663"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30292-4"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.75.6155"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607303"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.1014"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.78.9909"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1810527"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.73.7585"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2025.10.005"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2025.3700"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3157"},{"key":"e_1_2_10_14_2","volume-title":"Kisquali 200mg Film Coated Tablets","author":"Novartis","year":"2017"},{"key":"e_1_2_10_15_2","unstructured":"Diseases Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases LiverTox: Clinical and Research Information on Drug-Induced Liver Injury 2012."},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609709"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094557"},{"key":"e_1_2_10_18_2","unstructured":"Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012andRoussel Uclaf Causality Assessment Method (RUCAM) in Drug Induced Liver Injury LiverTox: Clinical and Research Information on Drug-Induced Liver Injury 2019 https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK548272\/."},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.2024.2433368"}],"container-title":["Case Reports in Oncological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/crom\/2417755","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/crom\/2417755","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/crom\/2417755","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:41:56Z","timestamp":1785757316000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/crom\/2417755"}},"subtitle":[],"editor":[{"given":"Lipi","family":"Buch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/crom\/2417755"],"URL":"https:\/\/doi.org\/10.1155\/crom\/2417755","archive":["Portico"],"relation":{},"ISSN":["2090-6706","2090-6714"],"issn-type":[{"value":"2090-6706","type":"print"},{"value":"2090-6714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2417755"}}