Jair Bar1, Gal Markel2, Teodor Gottfried3, Ruth Percik4, Raya Leibowitz-Amit5, Raanan Berger5, Talia Golan5, Sameh Daher3, Alisa Taliansky3, Elizabeth Dudnik6, Katerina Shulman7, Damien Urban5, Amir Onn8. 1. Institute of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel. Electronic address: Bar.jair@gmail.com. 2. Sackler Faculty of Medicine, Tel Aviv University, Israel; Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Israel. 3. Institute of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. 4. Institute of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel; Institute of Endocrinology, Sheba Medical Center, Israel. 5. Institute of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel. 6. Thoracic Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Israel. 7. Hillel Yaffe Medical Center, Hadera, Israel. 8. Pulmonology Institute, Sheba Medical Center, Tel HaShomer, Ramat Gan, Israel.
Abstract
AIM: Immune-related toxicities of immune checkpoint inhibitors (CPIs) require prompt diagnosis and treatment. Atherosclerosis has an inflammatory component; we speculated this inflammation could be enhanced by CPIs. We aimed to evaluate the risk of acute vascular events (AVEs) on CPIs. METHODS: Patients treated by CPIs in Sheba Medical Center (Israel) between January 2015 and May 2018 were retrospectively identified from electronic medical records. AVEs were identified and verified by chart review. Age, sex, diabetes, hypertension, smoking, dyslipidemia, previous AVE, renal failure, cancer type and specific treatments were evaluated as potential risk factors. AVE rate on CPIs was compared with that on chemotherapy or on combined chemo-immunotherapy in patients with lung adenocarcinoma. Survival of patients with AVEs was compared with that of patients without AVEs. RESULTS: CPI was administered to 1215 patients. AVEs within six months after CPI initiation occurred in 2.6% (95% confidence interval [CI]: 1.8-3.6) of patients, more common than in later time periods. In lung adenocarcinoma, event rate was 5.2% (95% CI: 2.8-9.2). Lung adenocarcinoma, prior AVE, hypertension and dyslipidemia were correlated with AVEs. AVE rate in patients with non-small cell lung cancer adenocarcinoma was similar whether on chemotherapy or on CPI. Survival of patients with AVEs was worse than that of those without AVEs. CONCLUSION: The similarly increased rates of AVEs for patients on CPI, on chemotherapy or on both suggest that although CPI may not augment the risk of AVE over that of chemotherapy, it carries a similar and significant risk of such adverse event. Caution should be exercised for patients with risk factors for AVEs.
AIM: Immune-related toxicities of immune checkpoint inhibitors (CPIs) require prompt diagnosis and treatment. Atherosclerosis has an inflammatory component; we speculated this inflammation could be enhanced by CPIs. We aimed to evaluate the risk of acute vascular events (AVEs) on CPIs. METHODS:Patients treated by CPIs in Sheba Medical Center (Israel) between January 2015 and May 2018 were retrospectively identified from electronic medical records. AVEs were identified and verified by chart review. Age, sex, diabetes, hypertension, smoking, dyslipidemia, previous AVE, renal failure, cancer type and specific treatments were evaluated as potential risk factors. AVE rate on CPIs was compared with that on chemotherapy or on combined chemo-immunotherapy in patients with lung adenocarcinoma. Survival of patients with AVEs was compared with that of patients without AVEs. RESULTS:CPI was administered to 1215 patients. AVEs within six months after CPI initiation occurred in 2.6% (95% confidence interval [CI]: 1.8-3.6) of patients, more common than in later time periods. In lung adenocarcinoma, event rate was 5.2% (95% CI: 2.8-9.2). Lung adenocarcinoma, prior AVE, hypertension and dyslipidemia were correlated with AVEs. AVE rate in patients with non-small cell lung cancer adenocarcinoma was similar whether on chemotherapy or on CPI. Survival of patients with AVEs was worse than that of those without AVEs. CONCLUSION: The similarly increased rates of AVEs for patients on CPI, on chemotherapy or on both suggest that although CPI may not augment the risk of AVE over that of chemotherapy, it carries a similar and significant risk of such adverse event. Caution should be exercised for patients with risk factors for AVEs.
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