Dataset Information

Acute cardiac manifestations under immune checkpoint inhibitors-beware of the obvious: a case report.

ABSTRACT:

Background

Immune checkpoint inhibitors (ICI) have revolutionized the management of many cancer types by drastically improving the median survival rate of patients. However, this efficiency comes at the cost of a high rate of immune-related adverse events, including lethal cardiac manifestations. Rapidly fatal cases of ICI-induced myocarditis have been reported and drawn considerable attention over the past years. However, it is essential to bear in mind that not all cardiac events occurring under ICI therapy are necessarily myocarditis.

Case summary

A 61-year-old female treated with pembrolizumab for a stage IV melanoma was admitted for chest pain leading to the diagnosis of ICI-related myocarditis based on the description of a discrete left ventricular subepicardial late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. ICI were suspended and intravenous methylprednisolone initiated. A second line anti-MEK therapy was initiated. After a month of treatment, similar chest pain occurred. CMR revealed a midventricular stress cardiomyopathy and no LGE was detected. A posteriori interrogation revealed emotional stressors preceding both episodes. Review of the first CMR, performed 2 weeks after symptom onset, indicated a pattern compatible with the recovery phase of a stress cardiomyopathy and the presence of LGE was questioned. ICI were reintroduced without recurrence of cardiac events.

Discussion

Not all cardiac manifestations occurring under ICI therapy are drug-related adverse events, therefore differential diagnoses must systematically be considered as the contraindication of ICI may have a major impact on patient prognosis. Cardiac imaging should be performed early and plays a key role in the management strategy.

SUBMITTER: Arangalage D

PROVIDER: S-EPMC8374985 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Immune checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of metastatic melanoma. However, ICI are often associated with immune-related adverse events (IRAE) such as colitis, hepatitis, pancreatitis, hypophysitis, pneumonitis, thyroiditis, exanthema, nephritis, myositis, encephalitis, or myocarditis. Biomarkers associated with the occurrence of IRAE would be desirable. In the literature, there is only little data available and furthermore mostly speculative, especially in view of genetic alterations. Our major aim was to check for possible associations between NGS-based genetic alterations and IRAE. We therefore analyzed 95 melanoma patients with ICI and evaluated their NGS results. We checked the data in view of potential associations between copy number variations (CNVs), small variations (VARs), human leucocyte antigen (HLA), sex, blood count parameters, pre-existing autoimmune diseases and the occurrence of IRAE. We conducted a literature research on genetic alterations hypothesized to be associated with the occurrence of IRAE. In total, we identified 39 genes that have been discussed as hypothetical biomarkers. We compared the list of these 39 genes with the tumor panel that our patients had received and focused our study on those 16 genes that were also included in the tumor panel used for NGS. Therefore, we focused our analyses on the following genes: AIRE, TERT, SH2B3, LRRK2, IKZF1, SMAD3, JAK2, PRDM1, CTLA4, TSHR, FAN1, SLCO1B1, PDCD1, IL1RN, CD274, UNG. We obtained relevant results: female sex was significantly associated with the development of hepatitis, combined immunotherapy with colitis, increased total and relative monocytes at therapy initiation were significantly associated with the development of pancreatitis, the same, pre-existing autoimmune diseases. Further significant associations were as follows: HLA homozygosity (hepatitis), and VARs on SMAD3 (pancreatitis). Regarding CNVs, significant markers included PRDM1 deletions and IL1RN (IRAE), CD274 duplications and SLCO1B1 (hepatitis), PRDM1 and CD274 (encephalitis), and PRDM1, CD274, TSHR, and FAN1 (myositis). Myositis and encephalitis, both, were associated with alterations of PRDM1 and CD274, which might explain their joined appearance in clinical practice. The association between HLA homozygosity and IRAE was clarified by finding HLA-A homozygosity as determining factor. We identified several genetic alterations hypothesized in the literature to be associated with the development of IRAE and found significant results concerning pre-existing autoimmune diseases and specific blood count parameters. Our findings can help to better understand the development of IRAE in melanoma patients. NGS might be a useful screening tool, however, our findings have yet to be confirmed in larger studies.