| アブストラクト | INTRODUCTION: As chimeric antigen receptor T-cell therapies are becoming increasingly available in the armamentarium of the hematologist, there is an emerging need to monitor post-marketing safety. OBJECTIVE: We aimed to better characterize their safety profile by focusing on cytokine release syndrome and identifying emerging signals. METHODS: We queried the US Food and Drug Administration Adverse Event Reporting System (October 2017-September 2020) to analyze suspected adverse drug reactions to tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Disproportionality analyses (reporting odds ratio) were performed by comparing chimeric antigen receptor T-cell therapies with (a) all other drugs (reference group 1) and (b) other onco-hematological drugs with a similar indication, irrespective of age (reference group 2), or (c) restricted to adults (reference group 3). Notoriety was assessed through package inserts and risk management plans. Adverse drug reaction time to onset and cytokine release syndrome features were investigated. RESULTS: Overall, 3225 reports (1793 axi-cel; 1433 tisa-cel) were identified. The reported toxicities were mainly: cytokine release syndrome (52.2%), febrile disorders (27.7%), and neurotoxicity (27.2%). Cytokine release syndrome and neurotoxicity were often co-reported and 75% of the events occurred in the first 10 days. Disproportionalities confirmed known adverse drug reactions and showed unexpected associations: for example, axi-cel with cardiomyopathies (reporting odds ratio = 2.3; 95% confidence interval 1.2-4.4) and gastrointestinal perforations (2.9; 1.2-7.3), tisa-cel with hepatotoxicity (2.5; 1.1-5.7) and pupil disorders (15.3; 6-39.1). CONCLUSIONS: Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity. |
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| ジャーナル名 | Drug safety |
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| 投稿日 | 2022/7/14 |
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| 投稿者 | Fusaroli, Michele; Isgro, Valentina; Cutroneo, Paola Maria; Ferrajolo, Carmen; Cirillo, Valentina; Del Bufalo, Francesca; Raschi, Emanuel; Poluzzi, Elisabetta; Trifiro, Gianluca |
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| 組織名 | Department of Medical and Surgical Sciences, Pharmacology Unit, University of;Bologna, via Irnerio 48, Bologna, Italy.;Department of Diagnostics and Public Health, University of Verona, Verona, Italy.;Sicilian Regional Pharmacovigilance Centre, University Hospital of Messina,;Messina, Italy.;Regional Centre of Pharmacovigilance and Pharmacoepidemiology, Naples, Italy.;Department of Pediatric Hematology/Oncology, Cellular and Gene Therapy, IRCCS;Bambino Gesu Children's Hospital, Rome, Italy.;Bologna, via Irnerio 48, Bologna, Italy. elisabetta.poluzzi@unibo.it. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/35829913/ |
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