Nida Waheed1, Michael G Fradley2, David L DeRemer3,4, Ahmad Mahmoud5, Chintan P Shah6, Taimour Y Langaee3,7, Gloria P Lipori8,9, Keith March5, Carl J Pepine5, Rhonda M Cooper-DeHoff3,5,7, Yonghui Wu10, Yan Gong11,12,13. 1. Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. 2. Cardio-Oncology Center of Excellence, Division of Cardiology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, PO Box 100486, 1345 Center Drive, Gainesville, FL, 32610-0486, USA. 4. UF Health Cancer Center, Gainesville, Florida, USA. 5. Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, Florida, USA. 6. Division of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida, USA. 7. Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA. 8. UF Health, Gainesville, Florida, USA. 9. Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. 10. Health Outcome and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, Florida, USA. 11. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, PO Box 100486, 1345 Center Drive, Gainesville, FL, 32610-0486, USA. gong@cop.ufl.edu. 12. UF Health Cancer Center, Gainesville, Florida, USA. gong@cop.ufl.edu. 13. Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, Florida, USA. gong@cop.ufl.edu.
Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. METHODS: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. RESULTS: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). CONCLUSIONS: This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.
BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. METHODS: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida's Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. RESULTS: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). CONCLUSIONS: This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.
Authors: Samuel Peter Heilbroner; Reed Few; Judith Mueller; Jitesh Chalwa; Francois Charest; Somasekhar Suryadevara; Christine Kratt; Andres Gomez-Caminero; Brian Dreyfus; Tomas G Neilan Journal: J Immunother Cancer Date: 2021-10 Impact factor: 13.751