| 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). 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 = 1378, 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 99/1783 (5.5%) of the reports and 262/1783 (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. Note, 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. |
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| 投稿者 | Dolladille, Charles; Ederhy, Stephane; Ezine, Emilien; Choquet, Sylvain; Nguyen, Lee S; Alexandre, Joachim; Moslehi, Javid J; Dechartres, Agnes; Salem, Joe-Elie |
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| 組織名 | Department of Pharmacology, CHU de Caen, Caen, 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.;Department of Onco-Dermatology, CHU de Caen, Caen, France.;Department of Hematology, AP-HP, Pitie-Salpetriere Hospital, Paris, France.;CMC Ambroise Pare, Research & Innovation, Neuilly-sur-Seine, France.;Department of Pharmacology, AP-HP, Pitie-Salpetriere Hospital, CIC-1901, INSERM,;Sorbonne Universite, APHP.Sorbonne UNICO-GRECO Cardio-Oncology Program, Paris,;France.;Vanderbilt University Medical Center, Department of Medicine, Cardio-Oncology;Program, 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), CIC-1901,;F75013, Paris, France. |
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