Aim. To analyze the condition of the cardiovascular system in oncological patients receiving immune antitumor therapy with immune checkpoint inhibitors (CPIs) based on results of laboratory and instrumental examinations during a 3-month follow-up.Material and methods. This multicenter prospective observational study included 49 patients (25 men and 24 women aged 65.6±8.7 and 64.3±9.6 years, respectively). A laboratory screening (C-reactive proteins, troponin I, N-terminal pro-brain natriuretic peptide), EchoCG, and carotid ultrasound were performed for all patients. 27 patients were followed up at 3 months after the antitumor therapy initiation. Statistical analysis was performed with the StatPlus 8.0.3 software.Results. Incidence of cardiovascular complications was 16.3 %. The following significant changes in EchoCG parameters were observed: LV EF; (p=0.017), increased LV end-systolic volume (ESV) (р=0.023), and increased LV index of myocardial performance (LIMP; р=0.016). The degree of changes in ESV (ΔESV) depended on a history of chronic heart failure (р=0.03), whereas the degree of changes in EF (ΔEF) depended on the patient’s age at the initiation of antitumor therapy (р=0.006). Ultrasound showed an increase in maximum carotid stenosis (р=0.018).Conclusion. The study showed a high incidence of newly developed cardiovascular complications associated with the CPI treatment as well as the presence of changes in EchoCG parameters and data of carotid ultrasound.
The evolution of drug therapy in solid tumors primarily leads to the increase in cancer specific survival, but inevitably raises financial burden. So far, none of the countries can venture total reimbursement with all necessary contemporary drugs for all patients. Doubling of expenses for cancer drug therapy in Russia in 2019 allowed oncologists using the most expensive treatments in more than 70 % of patients.Purpose: To evaluate efficacy of various treatment types of non‑small cell lung cancer in real clinical setting.Material and methods. We included patients with histologically verified metastatic non‑small cell lung cancer without activating mutations treated with first or second line therapy in 2018 – 2019. In total 287 patients were included: 230 — for the first line efficacy analysis, 100 — for the second. Time to disease progression, overall survival and objective response rate were evaluated.Results. The use of checkpoint inhibitors in accordance with all actual recommendations (first line pembrolizumab monotherapy in PD-L1 > 50 %, chemoimmunotherapy in first line or monotherapy in the second line irrespectively to PD-L1 status) decreased one‑year mortality from 61 % in 2018 to 33 % in 2019, but significantly increased financial cost (p < 0.000). Moreover, checkpoint inhibitors in combination with chemotherapy irrespectively of PD-L1 expression increased response rate (from 10 % and 21 % for monotherapy and platinum doublet, respectively, to 33,2 % for chemoimmunotherapy). PD‑1 inhibitors as monotherapy increased median time to disease progression (4,1 and 6,2 months for monotherapy with chemotherapy and platinum doublet, respectively, to 6,5 months and not achieved for chemoimmunotherapy and monotherapy with checkpoint inhibitors).Conclusion. More than doubling of financial costs spent for non‑small cell lung cancer treatment allowed access to contemporary treatment for all patients. Such unprecedented measures significantly improved efficacy, including double decrease of one‑year mortality. Nevertheless, rational design of regional clinical guidelines interpretation is of great importance in accurate and effective use of the healthcare budget.
Immune checkpoint inhibitors are promising agents for anticancer therapy. But despite their high efficacy in the treatment of solid tumors, there is still a problem with immune-related adverse events, especially cardiovascular complications with a very high mortality rate. Myocarditis or ischemic heart disease progression is not the only possible cause of cardiovascular death in patients treated with checkpoint inhibitors. We report a case of a patient with mucinous carcinoma of the lung, with a previous history of hypertension and moderate left ventricular dysfunction. The patient was prescribed atezolizumab, but the first atezolizumab infusion resulted in the patient cardiovascular death. Postmortem histopathological evaluation of myocardium revealed several possible reasons for hemodynamic instability: tumor embolism of the coronary arteries, micrometastases of mucinous carcinoma in the myocardium, and myocarditis diagnosed by both Dallas and immunohistochemistry criteria. In addition, testing for expression of PD-L1 detected the high levels of membranous and cytoplasmic PD-L1 protein even in the myocardium area free from tumor cells. The present clinical case demonstrates a problem of cardiovascular death in patients treated with checkpoint inhibitors and actualizes the need for future research of potential risk factors for cardiovascular complications.
Progress in conservative anticancer treatment is associated with an increase in long-term side effects of drugs in patients with successfully treated oncology. Immune checkpoint-inhibitors (ICI) belongs to group of anticancer immunotherapy. The most life threating cardiovascular adverse event are Checkpoint-associated myocarditis. This review provides information about potential mechanisms of immune related adverse events of ICI, epidemiology and clinical features of Checkpoint-associated myocarditis.
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