| アブストラクト | AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy. |
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| 投稿者 | Moey, Melissa Y Y; Jiwani, Rahim A; Takeda, Kotaro; Prenshaw, Karyn; Kreeger, R Wayne; Inzerillo, John; Liles, Darla K; Marcu, C Bogdan; Lebrun-Vignes, Benedicte; Morris, D Lynn; Ardhanari, Sivakumar; Salem, Joe-Elie |
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| 組織名 | Department of Cardiovascular Sciences, East Carolina Heart Institute, Vidant;Medical Center/East Carolina University, 115 Heart Drive, Greenville, NC, 27834,;USA.;Department of Internal Medicine, Vidant Medical Center/East Carolina University,;Greenville, NC, USA.;Department of Pathology and Laboratory Medicine, Vidant Medical Center/East;Carolina University, Greenville, NC, USA.;Marion L. Shepard Cancer Center, Washington, NC, USA.;Department of Hematology and Oncology, Vidant Medical Center/East Carolina;University, Greenville, NC, USA.;Department of Pharmacology, Regional Pharmacovigilance Centre, Pitie-Salpetriere;Hospital, Sorbonne Universite, INSERM CIC-1901, AP-HP, Paris, France.;EA Epiderme-Epidemiology in Dermatology and Evaluation of Therapeutics,;Universite Paris-Est Creteil, Creteil, France.;UNICO-GRECO APHP.Sorbonne Cardio-Oncology Program, Sorbonne Universite, Paris,;France.;Division of Cardiovascular Medicine, Cardio-Oncology Program, Vanderbilt;University Medical Center, Nashville, TN, USA. |
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