ICI-related myocarditis: key insights from 23 cases treated between 2019-2023

Treatment with immune checkpoint inhibitors (ICI) has revolutionized oncological treatment, improving outcomes across a range of malignancies. ICI-related myocarditis (ICIrM) is an unusual but severe side effect with high reported mortality rate. Guidelines on how to manage and treat ICIrM are diverse, allowing various interpretations. Our hypothesis was that frequent biomarker screening throughout ICI treatment would result in higher detection of subclinical ICIrM.

To evaluate clinical management of ICIrM focusing on background characteristics, cardiovascular morbidity, symptoms, diagnostics, biomarker and ECG monitoring, and treatment.

We conducted a descriptive retrospective case series of all ICIrM cases identified at the cardiovascular department of the University Hospital 2019-2023, with a population of 23 patients. ICIrM cases were identified by diagnosis-codes (ICD) for myocarditis and included in the case series. All patient records were scrutinized in detail regarding variables listed above, and descriptive data was summarised.

Suspicion of ICIrM was raised due to increased plasma levels of biomarkers Troponin T and/or NTproBNP in 35% (n=8) patients, who did not experience any myocarditis symptoms. Biomarkers were checked as part of clinical routine before next ICI dose in 6 patients; in 2 patients it was discovered en passant. In a further 12 patients, suspicion was raised due to increased levels of biomarkers in combination with clinical symptoms. In 3 patients, suspicion of ICIrM was raised merely due to symptoms. Dyspnoea was the most frequent symptom (13 patients). Among the patients without symptoms, treatment with Solu-medrol was initiated in 6 out of 8 patients.

The median level of Troponin T at ICIrM suspicion among asymptomatic patients was 63 ng/L (range 41-206); whereas in all 23 patients, median Troponin T was 83 ng/L (range 12-577 ng/L). The median level of NTproBNP among asymptomatic patients was 1,331 ng/L (range 107-12,700 ng/L) compared to a median value of 1,365 ng/L (range 107-16,300 ng/L) in the entire cohort. Median time from start of ICI to ICIrM was 57 days (range 19-819 days). Magnetic resonance imaging confirmed diagnosis in all cases but one. For background characteristics, please see Table 1.

In 35% of the patients in this case series, suspicion of ICIrM was based solely on elevated biomarkers, indicating that early detection with biomarker screening is a valuable tool in finding subclinical cases. However, elevated cardiovascular biomarkers are common in this patient group and there could potentially be a risk of over-diagnosis and over-treatment. Prospective studies addressing this question are required. Time between ICI start and the diagnosis of ICIrM was long in some cases, indicating that monitoring long-term side effects should be taken into consideration. Dyspnoea in patients receiving ICI is a symptom requiring attention.

Background Characteristics