Cardiac dysfunction in patients with kidney cancer receiving immunotherapy

Introduction Immunotherapy is a crucial treatment modality for patients with renal cell carcinoma, presenting a significant therapeutic challenge due to immune-related adverse events (irAEs) that can affect any organ system. Cardiotoxicity is a rare, but highly lethal irAE, necessitating early detection and prompt intervention, often requiring multidisciplinary collaboration. Purpose This study aims to detect myocardial subclinical dysfunction in patients with renal cell carcinoma receiving immunotherapy. The prinicipal objective is to initiate appropriate interventions to mitigate irAEs before symptomatic or fatal outcomes. Early intervention, including therapy interruption or administration of immunosuppressive agents, may prevent permanent impairment and significantly reduce mortality. Methods The study was initiated in September 2023 and has currently enrolled 31 patients with renal cell carcinoma. The patients have been receiving immunotherapy, either as adjuvant monotherapy or the combination (ipilimumab+nivolumab or pembeolizumab + lenvatinib) in the first line setting. Laboratory assessments, performed pretreatment and every six weeks afterwars, included a basic mineralogram, liver and renal function tests, glycemia, cardiac biomarkers (NT-proBNP, troponin, myoglobin), and neopterin as a prognostic marker for renal patients. Additionally, lipid profiles (triglycerides, total cholesterol, LDL, and HDL) were measured to distinguish atherosclerotic heart impairment. Functional testing included monthly ECG and quarterly echocardiograms. Patient symptoms were continuously monitored. Based on the laboratory results and functional testing, patients were categorized into two groups according presence of subclinical cardiotoxicity. Results Among 31 patients, cardiac toxicity was detected in 6 asymptomatic patients. None of these patients experienced cardiotoxicity leading to death or serious sequelae. Two patients had a significant increase in cardiac biomarkers (myoglobin and troponin), and 3 patients had a drop in left ventricular ejection fraction. One patient had subclinical ECG changes (the results are given in Figure 1 and Figure 2). One of these 6 patients was diagnosed with myositis leading to the early treatment suspension and prevention of more serious impairment. Conclusion These findings suggest that subclinical myocardial damage may be more common than previously reported across various treatments. Routine myoglobin monitoring enabled early detection and intervention for immune-related myositis, preventing a fulminant disease course in one patient. Despite the small cohort size, regular cardiac marker monitoring has proven beneficial. Continued follow-up in a larger patient group is necessary to validate the benefits of routine cardiac screening in patients undergoing immunotherapy.Clinical table of CardioTox group. Boxplots of selected data