{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:16:09Z","timestamp":1786738569676,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"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. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chimeric antigen receptor T-cell (CAR-T) therapy, a rapidly emerging treatment for cancer that has gained momentum since its approval by the FDA in 2017, involves the genetic engineering of patients\u2019 T cells to target tumors. Although significant therapeutic benefits have been observed, life-threatening adverse pulmonary events have been reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using SAS 9.4 with MedDRA 26.1, we retrospectively analyzed data from the Food and Drug Administration\u2019s Adverse Event Reporting System (FAERS) database, covering the period from 2017 to 2023. The analysis included the Reporting Odds Ratio Proportional Reporting Ratio Information Component and Empirical Bayes Geometric Mean to assess the association between CAR-T cell therapy and adverse pulmonary events (PAEs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The FAERS database recorded 9,400 adverse events (AEs) pertaining to CAR-T therapies, of which 940 (10%) were PAEs. Among these CAR-T cell-related AEs, hypoxia was the most frequently reported (344 cases), followed by respiratory failure (127 cases). Notably, different CAR-T cell treatments demonstrated varying degrees of association with PAEs. Specifically, Tisa-cel was associated with severe events including respiratory failure and hypoxia, whereas Axi-cel was strongly correlated with both hypoxia and tachypnea. Additionally, other CAR-T therapies, namely, Brexu-cel, Liso-cel, Ide-cel, and Cilta-cel, have also been linked to distinct PAEs. Notably, the majority of these PAEs occurred within the first 30\u00a0days post-treatment. The fatality rates varied among the different CAR-T therapies, with Tisa-cel exhibiting the highest fatality rate (43.6%), followed by Ide-cel (18.8%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study comprehensively analyzed the PAEs reported in the FAERS database among recipients of CAR-T cell therapy, revealing conditions such as hypoxia, respiratory failure, pleural effusion, and atelectasis. These CAR-T cell therapy-associated events are clinically significant and merit the attention of clinicians and researchers.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1434231","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T19:07:14Z","timestamp":1724353634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["CAR-T therapy pulmonary adverse event profile: a pharmacovigilance study based on FAERS database (2017\u20132023)"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinya","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjiao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (Transcend NHL 001): a multicentre seamless design study","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3099","DOI":"10.1016\/j.jacc.2019.10.038","article-title":"Cardiovascular events among adults treated with chimeric antigen receptor T-cells (CAR-T)","volume":"74","author":"Alvi","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e136012","DOI":"10.1172\/jci.insight.136012","article-title":"A rational mouse model to detect on-target, off-tumor CAR T cell toxicity","volume":"5","author":"Castellarin","year":"2020","journal-title":"JCI Insight"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1079181","DOI":"10.3389\/fimmu.2022.1079181","article-title":"Serious adverse events and coping strategies of CAR-T cells in the treatment of malignant tumors","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"115300","DOI":"10.1016\/j.psychres.2023.115300","article-title":"Cardiovascular toxicity induced by SSRIs: analysis of spontaneous reports submitted to FAERS","volume":"326","author":"Chen","year":"2023","journal-title":"Psychiatry Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11899-023-00687-7","article-title":"CAR-T cell therapy: the efficacy and toxicity balance","volume":"18","author":"Chohan","year":"2023","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1161\/CIRCULATIONAHA.120.048100","article-title":"Chimeric antigen receptor T-cell therapy-associated cardiomyopathy in patients with refractory or relapsed non-Hodgkin lymphoma","volume":"142","author":"Ganatra","year":"2020","journal-title":"Circulation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1016\/j.ymthe.2023.06.006","article-title":"Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells","volume":"31","author":"Haas","year":"2023","journal-title":"Mol. Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S1470-2045(21)00591-X","article-title":"Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial","volume":"23","author":"Jacobson","year":"2022","journal-title":"Lancet Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e133","DOI":"10.1016\/S2352-3026(21)00369-0","article-title":"KIR2DS1-HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials","volume":"9","author":"Kaddu-Mulindwa","year":"2022","journal-title":"Lancet Haematol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/j.cell.2022.03.041","article-title":"Enhanced safety and efficacy of protease-regulated CAR-T cell receptors","volume":"185","author":"Labanieh","year":"2022","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transpl."},{"key":"B13","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jaccao.2020.04.012","article-title":"Cardiovascular effects of CAR T cell therapy: a retrospective study","volume":"2","author":"Lefebvre","year":"2020","journal-title":"JACC CardioOncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1182\/blood.2021011898","article-title":"Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells","volume":"138","author":"Lichtenstein","year":"2021","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1200\/JCO.22.00842","article-title":"Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed\/refractory multiple myeloma: CARTITUDE-1 2-year follow-up","volume":"41","author":"Martin","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s40261-017-0503-6","article-title":"Can disproportionality analysis of post-marketing case reports be used for comparison of drug safety profiles?","volume":"37","author":"Michel","year":"2017","journal-title":"Clin. Drug Investig."},{"key":"B18","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1056\/NEJMoa2024850","article-title":"Idecabtagene vicleucel in relapsed and refractory multiple myeloma","volume":"384","author":"Munshi","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.2147\/ITT.S202015","article-title":"Cytokine release syndrome: current perspectives","volume":"8","author":"Murthy","year":"2019","journal-title":"ImmunoTargets Ther."},{"key":"B20","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrclinonc.2017.148","article-title":"Chimeric antigen receptor T-cell therapy - assessment and management of toxicities","volume":"15","author":"Neelapu","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1056\/NEJMoa1709919","article-title":"Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia","volume":"378","author":"Park","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma","volume":"380","author":"Schuster","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e001159","DOI":"10.1136\/jitc-2020-001159","article-title":"Impact of cytokine release syndrome on cardiac function following CD19 CAR-T cell therapy in children and young adults with hematological malignancies","volume":"8","author":"Shalabi","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1148\/radiol.2021210760","article-title":"Imaging-based toxicity and response pattern assessment following CAR T-cell therapy","volume":"302","author":"Smith","year":"2022","journal-title":"Radiology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.ccell.2019.02.003","article-title":"Logic-gated ROR1 chimeric antigen receptor expression rescues T cell-mediated toxicity to normal tissues and enables selective tumor targeting","volume":"35","author":"Srivastava","year":"2019","journal-title":"Cancer Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1182\/blood-2018-10-881722","article-title":"GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts","volume":"133","author":"Sterner","year":"2019","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","first-page":"851246","DOI":"10.3389\/fphar.2022.851246","article-title":"Adverse event profiles of PARP inhibitors: analysis of spontaneous reports submitted to FAERS","volume":"13","author":"Tian","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"731757","DOI":"10.3389\/fphar.2021.731757","article-title":"Pharmacovigilance bibliometrics: visualizing thematic development in the category of pharmacology and pharmacy in Web of Science","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2594","DOI":"10.1200\/JCO.22.01797","article-title":"Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: results from the US lymphoma CAR T Consortium","volume":"41","author":"Wang","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"925377","DOI":"10.3389\/fphar.2022.925377","article-title":"GLP-1 receptor agonist-associated tumor adverse events: a real-world study from 2004 to 2021 based on FAERS","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jaip.2020.09.021","article-title":"Emerging causes of drug-induced anaphylaxis: a review of anaphylaxis-associated reports in the FDA Adverse Event Reporting System (FAERS)","volume":"9","author":"Yu","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1434231\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T19:07:19Z","timestamp":1724353639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1434231\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,21]]},"references-count":32,"alternative-id":["10.3389\/fphar.2024.1434231"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1434231","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,21]]},"article-number":"1434231"}}