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. 2021 Dec 15;11(12):6074-6085.
eCollection 2021.

Real-world cardiovascular toxicity of immune checkpoint inhibitors in cancer patients: a retrospective controlled cohort study

Chuan Zhang  1 , Zhulu Chen  1 , Chunhua Mo  1 , Diansha Gao  1 , Yuxi Zhu  1 , Shu Qin  1 , Zhong Zuo  1
Affiliations

Real-world cardiovascular toxicity of immune checkpoint inhibitors in cancer patients: a retrospective controlled cohort study

Chuan Zhang et al. Am J Cancer Res. .

Abstract

Over the past decade, immune checkpoint inhibitors (ICI) have dramatically improved the prognosis of many cancer patients, but many immune-related adverse cardiovascular events (ACEs) have been observed. We aimed to investigate the occurrence of ACEs in the real world after receiving ICI and provide clinical reference for how to evaluate it. The study retrospectively included 204 patients who received ICI from October 2019 to November 2020 and 205 patients who only received traditional chemotherapy. The mean duration of follow-up for ICI group was 4.88 months, and the control group was 4.79 months. Patients in the control group did not develop myocarditis, only 2 cases of new-onset pericardial effusion occurred. In contrast, among ICI group, there were 3 cases of ICI-associated myocarditis, accounting for 1.47% (3/204), 6 cases of pericardial effusion. The incidence of new-onset ECG abnormalities in the ICI group was significantly higher than that of the control group (38/180 VS 16/178, HR 2.71, 95% CI: 1.449-5.067, P=0.001). In the ICI group, after receiving ICI treatment, cardiac biomarkers including average cardiac troponin T and N terminal pro B type natriuretic peptide increased significantly, peak in about 1 month, and then gradually decreasing. After the third or fourth month, the cardiac biomarkers gradually increased again. In conclusion, ICI may lead to various ACEs, and its incidence is higher than that of patients who only receive traditional chemotherapy. The changing trend of cardiac biomarkers reflects that ICI may cause acute and chronic myocardial damage. Regularly performing ECG, echocardiogram and cardiac biomarker examinations are helpful for early detection of ACEs caused by ICI and providing timely treatment.

Keywords: Immune checkpoint inhibitors (ICI); adverse cardiovascular events; cardiac biomarker; immunotherapy; myocarditis.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
A consort flow diagram of cohort. A total of 232 patients received ICI treatment, and a total of 204 patients met the inclusion criteria and were included in the ICI group. After screening, a total of 205 patients who received traditional chemotherapy at the same time were included in the control group.
Figure 2
Figure 2
Changes of cTnT in 3 patients with myocarditis before and after receiving carrelizumab and glucocorticoid. After receiving carrelizumab treatment, the cTnT of case 2 increased slightly, the cTnT of case 1 and case 3 both increased significantly within 1 month, and the troponin decreased significantly after methylprednisolone treatment.
Figure 3
Figure 3
Changes of NT-proBNP before and after treatment with carrelizumab and glucocorticoid in case 2. NT-proBNP increased sharply 24 days after receiving carrelizumab treatment, and decreased after receiving methylprednisolone treatment.
Figure 4
Figure 4
The ECG changes before and after ICI treatment in case 1. Left: before receiving Carrelizumab; Middle: day 24 after receiving Carrelizumab, ECG examination showed abnormal ST-T; Right: day 29 after receiving carrelizumab (5 days after receiving glucocorticoid), ECG shows that ST-T abnormality has returned to normal.
Figure 5
Figure 5
Myocardial T2 mapping by CMR in case 3. 39 days after receiving Carrelizumab, CMR showed an increase in the T2 value of the ventricular septum, which indicated local edema of the myocardium.
Figure 6
Figure 6
Changes of cTnT and NT-proBNP at baseline and after receiving anti-tumor drug treatment in control group (group 1) and ICI group (group 2).
See this image and copyright information in PMC

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