P3.02c-077 Cardiac Troponin-I Elevation in Patients with Non-Small Cell Lung Cancer during PD1/PDL1 Inhibition with Nivolumab: Topic: IT Biomarkers

Abstract

Immune check-point inhibitors are effective for the treatment of advanced non-small cell lung cancer (NSCLC); however, their mechanism of action is associated with peculiar immune-related adverse events (irAEs). While cardiac irAEs are seldom reported, animal data suggest that the myocardium might be sensitive to PD1/PD-L1 impairment. Minimal alterations of Cardiac Troponin-I (CTnI) can identify subclinical cardio-toxicity induced by antineoplastic agents like anthracyclines. The aim of this study is to determine whether CTnI might be used as a biomarker of cardiologic irAEs during treatment with nivolumab in advanced NSCLC. Serum samples were collected and stored from 61 patients receiving nivolumab (3 mg/Kg every 14 days) for advanced NSCLC within a single-institutional translational research study conducted in the San Martino Hospital – National Institute for Cancer Research, Genova, Italy (approved by the local ethical committee); samples were collected at baseline and at each cycle up to 5 cycles, and then every 2 cycles. Cardiac Troponin-I was retrospectively quantified with the luminescent oxygen channeling immunoassay (LOCI™) optimized on the Dimension Vista® analytical platform (Siemens Healthcare, Milan, Italy); and defined as undetectable (<0.015 μg/L) or detectable (>0.015 μg/L); a value of 0.045 μg/L was considered significant. Cardiologic anamnesis of the patients with detectable CTnI was collected from clinical documentation; additionally, patients alive at the time of the analysis underwent cardiologic evaluation. Fifty-nine patients were evaluable: median age= 69 years (44-81); male/female: 69%/31%; current or former smokers= 86.4%; non-squamous/squamous histology= 80%/20%; median number of cycles= 6 (1-29). Twenty-six out of 351 collected samples had detectable CTnI levels. Thirteen patients (22%) had detectable CTnI levels in at least one sample; among these, 6 (10%) patients had significant alterations in at least one sample, and in 3 cases (5%) this alteration was reported in multiple samples. No specific time-related pattern was identifiable for CTnI alterations. Five patients with detectable CTnI, of which 2 with significant alterations (0.292 μg/L and 0.285 μg/L), had neither evident cardiovascular disease, nor cancer-related para-cardiac infiltration. Two patients had pericardial effusion, while two other had concurrent irAEs (hyperthyroidism and hepatitis). Troponin-I was altered in a considerable number of patients receiving nivolumab, in some cases with no evident concurrent cardiovascular disease or manifest indirect noxae. Although a rationale for immunotherapy-related myocardial inflammation is acknowledged, further investigations on the cardiovascular effects of PD1/PDL1 inhibitors are required to draw meaningful conclusions, such as studies involving prospective cardiovascular assessments of patients receiving these agents.