| アブストラクト | The U.S. Food and Drug Administration (FDA) approved the first chimeric antigen receptor T-cell therapy, tisagenlecleucel, in August 2017. We sought to describe adverse events (AEs) reported to the FDA Adverse Event Reporting System (FAERS) for tisagenlecleucel in the post-marketing period. We searched FAERS reports to identify U.S. patients treated with tisagenlecleucel between August 30, 2017-August 31, 2019. We reviewed individual reports, calculated AE frequencies and reporting rates (RRs), and used Empirical Bayesian Geometric Mean methods to identify disproportionate reporting. We identified 646 de-duplicated reports with a median age at AE of 18 (interquartile range: 11-56) years. The overall RR was 81.0%, and more than 95% of reports described a serious outcome. Cytokine release syndrome (CRS) was the most frequently reported AE (51.1%) with a RR of 41.4%; neurotoxicity was reported less frequently (21.2%), with a RR of 17.2%. Most disproportionately reported AEs were listed on the package insert or confounded by indication. We identified 13 subsequent neoplasms (SPN), the majority occurring within 6 months of tisagenlecleucel administration, and none reporting evidence of insertional mutagenesis. A total of 165 reports (26%) described a death outcome; most deaths occurred >30 days after treatment. The majority of deaths (64%) were due to progression of the underlying lymphoid neoplasm, and few (<5%) were attributed to CRS or neurotoxicity. We did not identify new safety concerns reported for tisagenlecleucel in the post-marketing period. Reporting rates for CRS and neurotoxicity were lower than identified in the prelicensure clinical trials. |
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| ジャーナル名 | American journal of hematology |
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| 投稿日 | 2021/5/30 |
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| 投稿者 | Dores, Graca M; Jason, Christopher; Niu, Manette T; Perez-Vilar, Silvia |
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| 組織名 | U.S. Food and Drug Administration, Center for Biologics Evaluation and Research,;Office of Biostatistics and Epidemiology, Silver Spring, Maryland, USA. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/34050534/ |
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