Case Report: Multiple Causes of Cardiac Death After the First Infusion of Atezolizumab: Histopathological and Immunohistochemical Findings

Abstract

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.

The Interplay Between Cardiovascular Disease and Lung Cancer

“…Also, treatments like the immunotherapy drug atezolizumab, used for NSCLC, have been linked to CAD, even though the primary risk with immunotherapy is myopericarditis. Autopsies of patients who passed away after receiving atezolizumab have shown instances of coronary artery tumor embolization [ 36 ]. On another note, certain tyrosine kinase inhibitors (TKIs), such as the EGFR inhibitor osimertinib, are known for their cardiotoxic effects but do not seem to significantly increase the risk of CAD [ 37 ].…”

Risk factors for cardiovascular adverse events from immune checkpoint inhibitors

“…Salem et al reported that mortality from myocarditis is as high as 50% (5). Ekaterina et al reported that a patient with previous hypertension and moderate left ventricular dysfunction died from severe adverse effects after the first infusion of atezolizumab, with a histopathological diagnosis of myocarditis, tumour coronary artery embolization, and micrometastases of myocardial mucus carcinoma; high expression of PD-1 in the myocardial area without tumour cells was also detected (6). Although the cause of death cannot be completely attributed to ICIs, judging from the histopathological diagnosis and the high detection results of PD-L1, the use of atezolizumab aggravated the patient's diagnosis and contribute to death.…”