{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:59:23Z","timestamp":1793055563166,"version":"4.5.0"},"reference-count":22,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"29","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,10,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute\u2013Cancer Therapy Evaluation Program for National Cancer Institute\u2013sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti\u2013programmed cell death protein-1 (anti\u2013PD-1)\/programmed cell death-ligand 1 (anti\u2013PD-L1) alone or with additional anticancer therapies. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of 6,925 participants received anti\u2013PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti\u2013PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being \u2265 grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti\u2013PD-(L)1 + targeted therapies compared with anti\u2013PD-(L)1 + anti\u2013cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti\u2013PD-(L)1-based combination therapies versus single-agent anti\u2013PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non\u2013ICI-based anticancer therapies with anti\u2013PD-(L)1 treatments is needed. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.22.00369","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T18:14:18Z","timestamp":1654366458000},"page":"3439-3452","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":82,"title":["Major Adverse Cardiac Events With Immune Checkpoint Inhibitors: A Pooled Analysis of Trials Sponsored by the National Cancer Institute\u2014Cancer Therapy Evaluation Program"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7622-720X","authenticated-orcid":false,"given":"Abdul Rafeh","family":"Naqash","sequence":"first","affiliation":[{"name":"Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"},{"name":"Medical Oncology\/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa Y.Y.","family":"Moey","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Vidant Medical Center\/East Carolina University, Greenville, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Wei","family":"Cherie Tan","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, The University of Maryland Marlene and Stewart Greenbaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-1927","authenticated-orcid":false,"given":"Mehak","family":"Laharwal","sequence":"additional","affiliation":[{"name":"Internal Medicine, Barnabas Health, Livingston, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4906-0106","authenticated-orcid":false,"given":"Nagabhishek","family":"Moka","sequence":"additional","affiliation":[{"name":"Appalachian Regional Healthcare Cancer Center, Hazard, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0555-8965","authenticated-orcid":false,"given":"Shanda","family":"Finnigan","sequence":"additional","affiliation":[{"name":"Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Murray","sequence":"additional","affiliation":[{"name":"Technical Resources International, Inc, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-773X","authenticated-orcid":false,"given":"Douglas B.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javid J.","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, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-9719","authenticated-orcid":false,"given":"Elad","family":"Sharon","sequence":"additional","affiliation":[{"name":"Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30608-9"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30533-6"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.02.037"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044703"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht210"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034497"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1109\/TVCG.2014.2346248"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01806"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049981"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013757"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_156686"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.45.4553"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1901677"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1177\/1078155217745144"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609214"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000000038"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001887"},{"key":"b19","first-page":"13","volume":"7","author":"Zhang RS","year":"2021","journal-title":"Cardiooncology"},{"key":"b20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.TPS3154"},{"key":"b21","volume-title":"Immune Checkpoint Inhibitor Toxicity (I-CHECKIT): A Prospective Observational Study","author":"Southwest Oncology Group"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.7268"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.22.00369","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T22:01:21Z","timestamp":1665007281000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.22.00369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,10]]},"references-count":22,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2022,10,10]]}},"alternative-id":["10.1200\/JCO.22.00369"],"URL":"https:\/\/doi.org\/10.1200\/jco.22.00369","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,10]]},"assertion":[{"value":"2022-02-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-25","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}