{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T08:56:22Z","timestamp":1780995382318,"version":"3.54.1"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Immune checkpoint inhibitors are new immunotherapy drugs globally used for many malignancies, including renal cell carcinoma. Myocarditis as an immune-related adverse event is rare but highly fatal, suggesting that its frequency may be higher than reported. This paper describes a case of myocarditis that developed asymptomatically following ipilimumab and nivolumab combination therapy for renal cell carcinoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 71-year-old Asian man who presented to hospital with fever, fatigue, and weight loss of approximately 10\u00a0kg within 2\u00a0months was diagnosed with Xp.11.2 translocation renal cell carcinoma. Computed tomography revealed multiple lung masses, mediastinal lymph node enlargement, and a level II tumor thrombus reaching the inferior vena cava (cT3bN0M1; International Metastatic Renal Cell Carcinoma Database Consortium, poor risk). Ipilimumab\/nivolumab combination therapy was started as induction therapy. The patient experienced acute interstitial nephritis as an immune-related adverse event after treatment initiation; however, a good response to steroid therapy was observed. The antitumor effect of the immunotherapy was notable. Although he experienced pulmonary embolism, it seemed asymptomatic and harmless; thus, a second infusion was introduced. From the eighth day, he demonstrated rapidly worsening cardiogenic shock with asymptomatic electrocardiographic changes and drastic drop in cardiac biomarkers, and a diagnosis of myocarditis as an immune-related adverse event was made. Although immediate methylprednisolone mini-pulse therapy followed by tapered prednisolone prevented mortality, extensive myocardial fibrosis with marked ejection fraction decline persisted as a sequela. Consequently, follow-up without treatment was instituted; however, much of the tumor response initially observed was maintained over several months.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Physicians treating patients with immune checkpoint inhibitors should be aware of their potentially life-threatening cardiotoxic effects. This study emphasized the importance of a high index of suspicion, prompt diagnosis, and early intervention in patients who present with cardiac abnormalities and possible myocarditis after receiving immunotherapy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13256-021-03097-6","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T23:06:58Z","timestamp":1634252818000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Myocarditis as an immune-related adverse event following treatment with ipilimumab and nivolumab combination therapy for metastatic renal cell carcinoma: a case report"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8328-2255","authenticated-orcid":false,"given":"Yasuyuki","family":"Miyauchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohito","family":"Naito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsunemori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Tani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hasui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Minamino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Kushida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiji","family":"Haba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"3097_CR1","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1056\/NEJMoa1712126","volume":"378","author":"RJ Motzer","year":"2018","unstructured":"Motzer RJ, Tannir NM, McDermott DF, Frontera OA, Melichar B, Choueiri TK, et\u00a0al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277\u201390. https:\/\/doi.org\/10.1056\/NEJMoa1712126.","journal-title":"N Engl J Med"},{"key":"3097_CR2","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","volume":"4","author":"DY Wang","year":"2018","unstructured":"Wang DY, Salem J-E, Cohen JV, Chandra S, Menzer C, Ye F, et\u00a0al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4:1721\u20138. https:\/\/doi.org\/10.1001\/jamaoncol.2018.3923.","journal-title":"JAMA Oncol"},{"key":"3097_CR3","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1159\/000498985","volume":"1121","author":"N Agrawal","year":"2019","unstructured":"Agrawal N, Khunger A, Vachhani P, Colvin TA, Hattoum A, Spangenthal E, et\u00a0al. Cardiac toxicity associated with immune checkpoint inhibitors: case series and review of the literature. Case Rep Oncol. 2019;1121:260\u201376. https:\/\/doi.org\/10.1159\/000498985.","journal-title":"Case Rep Oncol"},{"key":"3097_CR4","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1056\/NEJMoa1609214","volume":"375","author":"DB Johnson","year":"2016","unstructured":"Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et\u00a0al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375:1749\u201355. https:\/\/doi.org\/10.1056\/NEJMoa1609214.","journal-title":"N Engl J Med"},{"key":"3097_CR5","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1016\/S1470-2045(18)30608-9","volume":"19","author":"J-E Salem","year":"2018","unstructured":"Salem J-E, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, et\u00a0al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19:1579\u201389. https:\/\/doi.org\/10.1016\/S1470-2045(18)30608-9.","journal-title":"Lancet Oncol"},{"key":"3097_CR6","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.jacc.2018.02.037","volume":"71","author":"SS Mahmood","year":"2018","unstructured":"Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et\u00a0al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71:1755\u201364.","journal-title":"J Am Coll Cardiol"},{"key":"3097_CR7","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1634\/theoncologist.2018-0157","volume":"23","author":"TG Neilan","year":"2018","unstructured":"Neilan TG, Rothenberg ML, Amiri-Kordestani L, Sullivan RJ, Steingart RM, Gregory W, et\u00a0al. Myocarditis associated with immune checkpoint inhibitors: an expert consensus on data gaps and a call to action. 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A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"508"}}