Myocarditis related to immune checkpoint inhibitors treatment: two case reports and literature review

Abstract

Immune checkpoint inhibitors can cause immune-related toxicity in various systems, and myocarditis is the most serious life-threatening toxicity. This report introduces diagnosis and treatment of two cases which developed myocarditis after receiving PD-1 inhibitors therapy. The first case was a 77-yearold male with chordoma, who was treated by third-line sintilimab combined with anlotinib, and presented with symptoms of chest tightness, shortness of breath and upper eyelid ptosis three weeks later. He was diagnosed as immune-checkpoint-inhibitors-related myocarditis and myositis-myasthenia-gravis overlap syndrome based on his clinical symptoms, serum biomarkers, electrocardiogram, echocardiogram, and characteristic findings on cardiac 18F-FDG PET-MRI. Methylprednisolone was given 480 mg/d initially and was gradually reduced to 40 mg/d in 4 weeks, with the myocardial injury biomarkers declined in the same time. The second case was a 69-year-old female with advanced non-small cell lung cancer, who was treated by pemetrexed combined with bevacizumab and camrelizumab, and presented with palpitations 20 days later. She was diagnosed as immune-checkpoint-inhibitors-related myocarditis based on her clinical symptoms, serum biomarkers, electrocardiogram and echocardiogram. Methylprednisolone was given 240 mg/d initially and was gradually reduced to 40 mg/d with good response of myocardial injury biomarkers decline.However, the patient developed fatal myasthenia gravis afterwards, with little response to all treatments. These two cases revealed that, early detection and timely intervention, including discontinuation of immune checkpoint inhibitors and initiation of adequate steroid therapy, can reduce morbidity and mortality and improve prognosis.

Intrinsic Differences in Immune Checkpoint Inhibitor-Induced Myocarditis: A Retrospective Analysis of Real World Data

“…We searched PubMed for relevant articles to validate our findings and selected 30 patients for analysis ( Katsume et al, 2018 ; Khoury et al, 2019 ; Wang and Hu, 2019 ; Balanescu et al, 2020 ; Diamantopoulos et al, 2020 ; Hardy et al, 2020 ; Hyun et al, 2020 ; Leaver et al, 2020 ; Szuchan et al, 2020 ; Tu et al, 2020 ; Valenti-Azcarate et al, 2020 ; Wang et al, 2020 ; Xie et al, 2020 ; Xing et al, 2020 ; Arangalage et al, 2021 ; Cham et al, 2021 ; Chen et al, 2021 ; Elder et al, 2021 ; Iwasaki et al, 2021 ; Komatsu et al, 2021 ; Liang et al, 2021 ; Tanabe et al, 2021 ; Yanase et al, 2021 ; Zhang et al, 2021 ). The results are coincident with ours.…”

Camrelizumab-Related Myocarditis and Myositis With Myasthenia Gravis: A Case Report and Literature Review

“…Thirty-two percent of myositis patients had myocarditis (n = 6), 5% of myositis patients had MG, and two patients died from myositis, which is consistent with findings from a WHO registry: myocarditis was associated with myositis in 25% of cases and with MG in 11% of cases. A death case of MG with immunerelated myositis involving the myocardium has been reported after camrelizumab treatment (25). Surprisingly, MG also occurred concomitantly in 11 (10%) of 101 patients with myocarditis (26).…”

Sintilimab induced ICIAM in the treatment of advanced HCC: A case report and analysis of research progress

“…Huan Bi et al reported a case with lung squamous cell carcinoma (SCC) that developed ICIAM within 6 days plus three cycles after receiving sintilimab treatment (21 days/cycle) (14). Chen and Liang et al reported the case of ICIAM in a chordoma patient who received sintilimab plus anlotinib treatment respectively (15,16). The retrospective analysis of cases from 12 cancer treatment centers in China by Wang et al showed that the incidence of ICIAM in China was about 1.05%, the median time of occurrence was 38 d, and 81.2% occurred in the first or second cycle of ICIs therapy with a high mortality rate.…”