The Characteristics of Cardiovascular Adverse Events in Therapy with Immune Checkpoint Inhibitors: The Result of Work of the Multi-Disciplinary Team

Abstract

Introduction. In order to assess the nature and frequency of cardiovascular adverse events (CVAE) occurring against the background of therapy with immune checkpoint inhibitor (ICI) in comparison with that which occurs during treatment of cancer patients with known cardiotoxic chemotherapy drugs, an open observational retrospective and prospective study was conducted on the basis of an oncological department in a multidisciplinary medical institution.

Materials and Methods. The study included two groups: 88 patients receiving ICI therapy and 102 patients receiving chemotherapy with cardiotoxic chemotherapy drugs. Diagnostic tests were carried out, including cardiac markers, ECG, 24-hour ECG monitoring and echocardiography. In the event of acute cardiotoxic AEs, cardiac magnetic resonance imaging, coronary angiography, ventriculography and angiography of peripheral arteries were performed for differential diagnosis of cardiovascular immune AEs. The standard statistical analysis was conducted using the Chi-square test and Mann-Whitney test.

Results. During antitumor treatment, various cardiovascular AEs such as acute coronary syndrome, heart failure, arrhythmias, complications contributing to indirect cardiotoxicity - deterioration of renal function, thyroid gland disorders and death from non-cardiovascular causes in groups of immunotherapy and cardiotoxic chemotherapy occurred with approximately equal frequency. A total of 109 complications (mean 1.9 AEs) were identified in 58 patients (65.9 %) in the immunotherapy group and 110 AEs in 60 patients (58.8 %, mean 1.8 AEs) in the chemotherapy group. Myocarditis was diagnosed in 5.6 % of cases, death from cardiovascular causes in 5.6 %, and pericarditis in 3.4 %. These complications were observed only in the ICI treatment group.

Conclusion. Therapy with drugs from the ICI group can be classified as cardiotoxic antitumor therapy, since the incidence of cardiovascular complications during immunotherapy is comparable to that of cardiotoxic chemotherapy. The causes of cardiovascular AEs are not always immune-mediated. They may occur due to worsening of cardiovascular diseases, indirect cardiotoxicity, or the course of the oncological process itself. Therefore, timely diagnosis, prevention strategies, treatment of cardiovascular disorders, and further management of patients are required. To achieve these goals, it is necessary to form interdisciplinary teams with cardiologists/cardio-oncologists and specialists from other areas participating in the work of multidisciplinary consultations.