{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T10:24:21Z","timestamp":1781951061019,"version":"3.54.5"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs), including PD-1 inhibitors, have significantly improved survival outcomes in patients with melanoma; however, serious adverse events may occur as a consequence of immune dysregulation. Autoimmune hemolytic anemia (AIHA) is a rare but potentially life-threatening condition. While corticosteroids remain the cornerstone of AIHA management, some patients with severe anemia require additional immunosuppressive agents beyond steroids alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>A 52-year-old woman with anal canal malignant melanoma presented with severe generalized fatigue, lower back pain, and gross hematuria. She had received one cycle of pembrolizumab two weeks prior to presentation. She had severe anemia with reticulocytosis, elevated lactate dehydrogenase and bilirubin levels, and a positive direct Coombs test, and was diagnosed with severe AIHA secondary to pembrolizumab therapy. Despite initial treatment with corticosteroids and intravenous immunoglobulin (IVIG), hemolysis progressed. The condition was ultimately controlled with cyclophosphamide (CTX) and fluorouracil (5-FU) in addition to corticosteroids. Three months later, pembrolizumab was again administered and the resulting AIHA was managed with corticosteroids alone. The patient subsequently completed cycles 3\u20138 of pembrolizumab without further recurrence and achieved sustained tumor control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case illustrates a novel immunosuppressive strategy for management of pembrolizumab-induced AIHA, a rare but serious hematologic adverse effect associated with immunotherapy. We describe the clinical presentation and report that the combination of CTX and 5-FU in addition to corticosteroids and IVIG was successful in treating severe AIHA. Further investigation in larger cohorts is warranted to validate this approach for intervention in AIHA. With appropriate and prompt management, safe rechallenge and continuation of ICIs may be feasible in selected patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1811425","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:51:53Z","timestamp":1778219513000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Severe immune-related autoimmune hemolytic anemia induced by pembrolizumab: a case report with novel immunosuppressive strategy"],"prefix":"10.3389","volume":"17","author":[{"given":"Qin","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Oncology, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, People\u2019s Hospital of Xinjin","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Oncology, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)01206-x","article-title":"Immune checkpoint inhibitors in melanoma","volume":"398","author":"Carlino","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s40364-025-00807-w","article-title":"T cells in cancer: mechanistic insights and therapeutic advances","volume":"13","author":"Pu","year":"2025","journal-title":"biomark Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.11.016","article-title":"Immune-related adverse events with immune checkpoint blockade: a comprehensive review","volume":"54","author":"Michot","year":"2016","journal-title":"Eur J Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s10875-025-01929-4","article-title":"The targets of immune adverse events in cancer immunotherapy by combined check-point inhibitors resemble those seen in IPEX patients","volume":"45","author":"Moraes-Fontes","year":"2025","journal-title":"J ClinImmunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2021.11.002","article-title":"Immunotherapy-associated autoimmune hemolytic anemia","volume":"36","author":"Hwang","year":"2022","journal-title":"Hematol Oncol Clin North Am"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2025031449","article-title":"Immune thrombocytopenia in patients treated with immune checkpoint inhibitors","volume":"147","author":"Leaf","year":"2026","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.03.008","article-title":"European consensus-based interdisciplinary guideline for melanoma. 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