|アブストラクト||Chimeric-Antigen-Receptor T-Cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel-T). We conducted a Bayesian disproportionate analysis with the 95% lower credibility-interval of information component (IC025 , significance>0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. |
Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n=1,378, IC025 =4.24), neurological disorders (n=963, IC025 =2.42), hematological disorders (n=532, IC025 =3.32), infections (n=287, IC025 =2.38), cardiovascular disorders (n=256, IC025 =2.81), pulmonary disorders (n=186, IC025 =3.80), reno-metabolic disorders (n=123, IC025 =1.89), hemophagocytic-lymphohistiocytosis (n=36, IC025 =5.01) and hepatic disorders (n=32, IC025 =2.49). ADR-related fatalities accounted for 99/1,783 (5.5%) of the reports and 262/1,783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny. This article is protected by copyright. All rights reserved.
|投稿者||Dolladille, Charles; Ederhy, Stephane; Ezine, Emilien; Choquet, Sylvain; Nguyen, Lee S; Alexandre, Joachim; Moslehi, Javid J; Dechartres, Agnes; Salem, Joe-Elie|
|組織名||CHU de Caen, Department of Pharmacology, Caen, F-14000, France, Universite Caen;Normandie, Medical School, EA 4650, Signalisation, Electrophysiologie et Imagerie;des Lesions d'Ischemie-reperfusion Myocardique, Caen, France.;Hopitaux Universitaires Paris-Est, Assistance Publique-Hopitaux de Paris, Hopital;Saint Antoine, Service de Cardiologie, Unico, Unite de Cardio-Oncologie APHP.6,;GRC, Groupe de Recherche Clinique en Cardio Oncologie, Inserm 856, Universite;Pierre et Marie Curie, Paris, France.;CHU de Caen, Department of Onco-dermatology, Caen, France.;AP-HP, Pitie-Salpetriere Hospital, Department of Hematology, Paris, France.;CMC Ambroise Pare, Research & Innovation, Neuilly-sur-Seine, France.;AP-HP, Pitie-Salpetriere Hospital, Department of Pharmacology, CIC-1901; INSERM,;Sorbonne Universite, APHP.Sorbonne UNICO-GRECO Cardio-oncology Program, Paris,;France.;Vanderbilt University Medical Center, Cardio-oncology program, Department of;medicine, Nashville, Tennessee, USA.;Sorbonne Universite, INSERM, Institut Pierre Louis d'Epidemiologie et de Sante;Publique, AP-HP.Sorbonne Universite, Hopital Pitie Salpetriere, Departement de;Sante Publique, Centre de Pharmacoepidemiologie de l'AP-HP (Cephepi), Paris,|