| アブストラクト | BACKGROUND: Chimeric antigen receptor T (CAR-T) cells have proven to be a game changer for treating several hematologic malignancies. Randomized controlled trials have highlighted potential life-threatening adverse drug reactions (ADRs), including cytokine release syndrome (CRS). Acute renal failure (ARF) has also been reported in 20% of the patients treated. However, an analysis of renal safety supported by large-scale real-life data seems warranted. PATIENTS AND METHODS: We queried VigiBase(R) for all reports of the Standardised MedDRA Query "acute renal failure" (ARF) involving a CAR-T cell, registered until 24 July 2022. Disproportionality for this ADR was analyzed through calculation of the Information Component [IC (95% confidence interval)]. A positive lower end of the 95% confidence interval of the IC is the threshold used in statistical signal detection in VigiBase(R). The same analysis was carried out for various hydroelectrolytic disorders. RESULTS: We gathered 224 reports of ARF, and 125 reports of hydroelectrolytic disorders involving CAR-T cells. CAR-T cells were disproportionately reported with ARF [IC 1.5 (1.3-1.7)], even after excluding reports mentioning CRS. A significant disproportionate reporting was also found for hypernatremia [IC 3.1 (2.2-3.8)], hyperphosphatemia [IC 3.1 (1.8-3.9)], hypophosphatemia [IC 2.0 (0.6-2.9)], metabolic acidosis [IC 1.8 (1.2-2.2)], hyponatremia [IC 1.6 (1.1-2.0)], and hypercalcemia [IC 1.4 (0.5-2.1)]. There was no disproportionate reporting of dyskalemia. CONCLUSIONS: This study is limited by the inherent flaws of pharmacovigilance approaches. Nonetheless, our findings suggest that ARF and an array of hydroelectrolytic disorders are potential ADRs of CAR-T cell therapy, in real-life settings and in a nonselected population. |
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| ジャーナル名 | BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy |
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| 投稿日 | 2023/5/11 |
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| 投稿者 | Gerard, Alexandre O; Merino, Diane; Charbinat, Alexis; Fournier, Joseph; Destere, Alexandre; Loschi, Michael; Cluzeau, Thomas; Sicard, Antoine; Drici, Milou-Daniel |
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| 組織名 | Department of Nephrology-Dialysis-Transplantation, University Hospital Centre of;Nice, Nice, France.;Department of Pharmacology and Pharmacovigilance, University Hospital Centre of;Laboratory of Molecular Physio Medicine (LP2M), UMR 7370, CNRS, University Cote;d'Azur, Nice, France.;Department of Hematology, University Hospital Centre of Nice, Nice, France.;Clinical Research Unit of University Cote d'Azur (UR2CA), University Cote d'Azur,;Nice, France.;Nice, Nice, France. pharmacovigilance@chu-nice.fr. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37166707/ |
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