{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:37:49Z","timestamp":1792575469304,"version":"4.5.0"},"reference-count":11,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"unspecified","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,3,17]]},"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:p>\n                    Immune-checkpoint inhibitors (ICI) have revolutionized cancer therapy but are associated with infrequent but lethal myocarditis, for which management remains uncertain. Abatacept, a CTLA-4 fusion protein targeting CD86 on antigen presenting cells and leading to global T-cell anergy, has been described as a potential treatment in individual reports. Yet, abatacept treatment dosage, schedule and optimal combination with other immunosuppressive therapies are unclear. We describe a 25-year-old man who developed pembrolizumab (anti-PD1)-induced myocarditis 14 days after first injection for thymoma treatment, which deteriorated into cardiogenic shock, with sustained ventricular arrhythmia, requiring urgent extracorporeal life support implantation, despite prompt initiation of corticosteroids and mycophenolate-mofetil. Using a strategy of serial measurement ensuring with a target of &gt;80%\u2009CD86 receptor occupancy on circulating monocytes, abatacept dose was adjusted and combined with ruxolitinib and methylprednisolone. This strategy resulted in high-dose of abatacept: 60\u2009mg\/kg in three doses (20\u2009mg\/kg each) within the first 10 days, followed by two doses. Clinical improvement occurred within 7\u2009days, with resolution of systolic cardiac dysfunction, and ventricular arrhythmias resulting in successful discharge from hospital. We reversed a case of nearly lethal ICI-myocarditis, using specific patient-dose adjusted abatacept, which may serve as basis for personalized treatment of patients with severe ICI-adverse events. Trial registration number:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04294771\">NCT04294771<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1136\/jitc-2022-004699","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T11:56:23Z","timestamp":1649159783000},"page":"e004699","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":103,"title":["Reversal of immune-checkpoint inhibitor fulminant myocarditis using personalized-dose-adjusted abatacept and ruxolitinib: proof of concept"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04294771","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6014-6269","authenticated-orcid":false,"given":"Lee S","family":"Nguyen","sequence":"first","affiliation":[{"name":"Research and Innovation of CMC Ambroise Par\u00e9 (RICAP), Centre Medico-Chirurgical Ambroise Par\u00e9, Neuilly-sur-Seine, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Bretagne","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UNICO-GRECO Cardio-Oncology Program, Sorbonne Universit\u00e9, INSERM CIC-1901, AP.HP.Sorbonne, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Arrondeau","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Cochin Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Zahr","sequence":"additional","affiliation":[{"name":"AP-HP, Inserm, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Department of Pharmacology, CIC-1901, Pharmacokinetics and Therapeutic Drug Monitoring Unit, UMR-S 1166, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0792-2521","authenticated-orcid":false,"given":"Stephane","family":"Ederhy","sequence":"additional","affiliation":[{"name":"Cardiology Department and Sorbonne Universit\u00e9, GRC n\u00b027, Groupe de Recherche en Cardio-Oncologie, AP-HP, H\u00f4pital Saint-Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baptiste","family":"Abbar","sequence":"additional","affiliation":[{"name":"INSERM, Institut Pierre Louis d'Epid\u00e9miologie et de Sant\u00e9 Publique (iPLESP), Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Piti\u00e9 Salp\u00eatri\u00e8re Hospital, Department of Medical Oncology, Institut Universitaire de Canc\u00e9rologie, CLIP2 Galil\u00e9e, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Pinna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UNICO-GRECO Cardio-Oncology Program, Sorbonne Universit\u00e9, INSERM CIC-1901, AP.HP.Sorbonne, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Allenbach","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology, Piti\u00e9 Salpetriere Hospital, APHP, INSERM, Sorbonne University, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Mira","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, Groupe Hospitalier Paris Centre, M\u00e9decine Intensive R\u00e9animation, Universit\u00e9 de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javid","family":"Moslehi","sequence":"additional","affiliation":[{"name":"Section of Cardio-Oncology & Immunology, Division of Cardiology and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Rosenzwajg","sequence":"additional","affiliation":[{"name":"INSERM UMRS_959; APHP. 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