{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:28:59Z","timestamp":1793348939612,"version":"4.5.0"},"reference-count":48,"publisher":"American Association for Cancer Research (AACR)","issue":"5","funder":[{"name":"No funding"}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Immune-checkpoint-inhibitor (ICI)\u2013associated myotoxicity involves the heart (myocarditis) and skeletal muscles (myositis), which frequently occur concurrently and are highly fatal. We report the results of a strategy that included identification of individuals with severe ICI myocarditis by also screening for and managing concomitant respiratory muscle involvement with mechanical ventilation, as well as treatment with the CTLA4 fusion protein abatacept and the JAK inhibitor ruxolitinib. Forty cases with definite ICI myocarditis were included with pathologic confirmation of concomitant myositis in the majority of patients. In the first 10 patients, using recommended guidelines, myotoxicity-related fatality occurred in 60%, consistent with historical controls. In the subsequent 30 cases, we instituted systematic screening for respiratory muscle involvement coupled with active ventilation and treatment using ruxolitinib and abatacept. The abatacept dose was adjusted using CD86 receptor occupancy on circulating monocytes. The myotoxicity-related fatality rate was 3.4% (1\/30) in these 30 patients versus 60% in the first quartile (P &amp;lt; 0.0001). These clinical results are hypothesis-generating and need further evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Early management of respiratory muscle failure using mechanical ventilation and high-dose abatacept with CD86 receptor occupancy monitoring combined with ruxolitinib may be promising to mitigate high fatality rates in severe ICI myocarditis.<\/jats:p>\n                    <jats:p>See related commentary by Dougan, p. 1040.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1027<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-22-1180","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T03:10:35Z","timestamp":1677121835000},"page":"1100-1115","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":243,"title":["Abatacept\/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis"],"prefix":"10.1158","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0331-3307","authenticated-orcid":false,"given":"Joe-Elie","family":"Salem","sequence":"first","affiliation":[{"name":"1Sorbonne Universit\u00e9, INSERM, UNICO-GRECO Cardio-oncology Program, Department of Pharmacology, GRC27, CIC-1901, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8170-9991","authenticated-orcid":false,"given":"Marie","family":"Bretagne","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, INSERM, UNICO-GRECO Cardio-oncology Program, Department of Pharmacology, GRC27, CIC-1901, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-8131","authenticated-orcid":false,"given":"Baptiste","family":"Abbar","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, INSERM, UNICO-GRECO Cardio-oncology Program, Department of Pharmacology, GRC27, CIC-1901, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."},{"name":"2Sorbonne Universit\u00e9, INSERM, Department of Oncology, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2365-7932","authenticated-orcid":false,"given":"Sarah","family":"Leonard-Louis","sequence":"additional","affiliation":[{"name":"3Sorbonne Universit\u00e9, INSERM, Department of Neuropathology, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0792-2521","authenticated-orcid":false,"given":"St\u00e9phane","family":"Ederhy","sequence":"additional","affiliation":[{"name":"4Sorbonne Universit\u00e9, INSERM, UNICO-GRECO Cardio-oncology Program, Department of Cardiology, GRC27, AP-HP, H\u00f4pital Saint-Antoine, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1002-9902","authenticated-orcid":false,"given":"Alban","family":"Redheuil","sequence":"additional","affiliation":[{"name":"5Sorbonne Universit\u00e9, INSERM, Institute of Cardiometabolism and Nutrition, Department of Radiology, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5489-452X","authenticated-orcid":false,"given":"Samia","family":"Boussouar","sequence":"additional","affiliation":[{"name":"5Sorbonne Universit\u00e9, INSERM, Institute of Cardiometabolism and Nutrition, Department of Radiology, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6014-6269","authenticated-orcid":false,"given":"Lee S.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"1Sorbonne Universit\u00e9, INSERM, UNICO-GRECO Cardio-oncology Program, Department of Pharmacology, GRC27, CIC-1901, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."},{"name":"6Research and Innovation of CMC Ambroise Par\u00e9 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France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2381-793X","authenticated-orcid":false,"given":"Aude","family":"Rigolet","sequence":"additional","affiliation":[{"name":"12Sorbonne Universit\u00e9, INSERM, Department of Internal Medicine, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-787X","authenticated-orcid":false,"given":"Perrine","family":"Guillaume-Jugnot","sequence":"additional","affiliation":[{"name":"12Sorbonne Universit\u00e9, INSERM, Department of Internal Medicine, AP-HP, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-0118","authenticated-orcid":false,"given":"Nicolas","family":"Champtiaux","sequence":"additional","affiliation":[{"name":"12Sorbonne Universit\u00e9, INSERM, Department 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