{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:34:55Z","timestamp":1777890895263,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Cancer Medicine"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune\u2010related hepatitis (ir\u2010hepatitis) is an immune\u2010related adverse event that can be resistant to systemic steroid therapy. Mycophenolate mofetil (MMF) is recommended for steroid\u2010refractory cases; however, evidence supporting its efficacy remains unclear. We aimed to evaluate the efficacy of MMF in patients with solid tumors, the optimal timing for administration, and its effect on cumulative steroid dosage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort analysis was conducted between January 2015 and August 2023. We obtained data from eligible consecutive patients who developed ir\u2010hepatitis with grade \u2265\u20092 alanine aminotransferase (ALT) elevation requiring systemic steroids. Participants were divided into three groups: MMF\u2010early combination, MMF\u2010late combination, and systemic steroid\u2010only. ALT improvement rate was used to assess the efficacy of MMF based on the Common Terminology Criteria for Adverse Events version 5.0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 4405 patients treated with immune checkpoint inhibitors, 151 (3.4%) developed ir\u2010hepatitis requiring systemic steroids, of whom 123 had grade \u2265\u20092 ALT elevation. The median patient age was 62\u2009years (interquartile range: 54\u201372), and 42 patients (34%) received MMF. Forty\u2010one patients were evaluable for MMF timing. The ALT improvement rate on day 7 was significantly higher in the MMF\u2010early combination group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910) than in the MMF\u2010late combination group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200931) (78.5% vs. 41.6%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Among 40 patients evaluable for steroid dosage, cumulative systemic steroid dosage was significantly lower in the MMF\u2010early combination group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) than in the MMF\u2010late combination group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200932) (2121\u2009mg vs. 3745\u2009mg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03). These effects were comparable even for the MMF\u2010early combination and systemic steroid\u2010only groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Despite the small sample size, early combination therapy with MMF and systemic steroids rapidly improved ir\u2010hepatitis, consequently reducing the cumulative systemic steroid dosage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71720","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T09:02:42Z","timestamp":1773910962000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Mycophenolate Mofetil Combination Therapy as an Effective Approach for Immune\u2010Related Hepatitis Induced by Immune Checkpoint Inhibitors in Patients With Solid Tumor"],"prefix":"10.1002","volume":"15","author":[{"given":"Yukiko Shimoda","family":"Igawa","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4896-5824","authenticated-orcid":false,"given":"Tatsuya","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"},{"name":"Department of Experimental Therapeutics National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Yoshinami","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Hibino","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamichi","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Pharmacy National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuta","family":"Maruki","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-5227","authenticated-orcid":false,"given":"Hirokazu","family":"Shoji","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2763-7346","authenticated-orcid":false,"given":"Kenjiro","family":"Namikawa","sequence":"additional","affiliation":[{"name":"Department of Dermatologic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Sudo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4209-4493","authenticated-orcid":false,"given":"Yoshitaka","family":"Honma","sequence":"additional","affiliation":[{"name":"Department of Head and Neck, Esophageal Medical Oncology National Cancer Center Hospital  Tokyo 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