Cardiotoxicity surveillance among patients with cancer treated with immunotherapy.
Authors: Fagundes Juliana Goes Martins , Torres Matheus Coelho , Sousa Thiago Lins Fagundes de , Botelho Luis Fabio , Figueiredo Eudanusia Guilherme de , Flamini Rodrigo de Carvalho , Lacerda Emilio Carlos De Arruda , Pereira Jean Fabrício De Lima , Duarte Igor Lemos , Castro Gilberto , de Melo Marcelo Dantas Tavares , Ferreira Silvia Moreira Ayub 
Published: June 2023

2636

Background: With the advancements of immunotherapy procedures and, more specifically, immunological checkpoint inhibitors (ICIs), the scenario of cancer treatment, whether in its early or advanced stages, have changed. With the expansion of ICIs usage, cardiovascular toxicities have been reported, but more robust data are needed to guide the follow-up of patients and toxicity prevention. Methods: This research is a single-centered, prospective observational cohort study that evaluated patients treated with ICIs regardless of indication, with or without chemotherapy combination. Patients underwent echocardiography evaluation with global longitudinal strain (GLS) and myocardial work, electrocardiogram, and collection of biomarkers before the start of treatment, in the second month after treatment started, and every 3 months, subsequently. Evaluations stopped once treatment completed one year, or the medication was discontinued either due to toxicity or disease progression. Cardiotoxicity (CT) was defined by ≥ 10% reduction in left ventricular ejection fraction (LVEF) by less than 50%, troponin elevation by ≥ 0,30 ng/ml, or reduction in relative GLS by ≥ 15%. Frequencies were compared using Fisher's comparative test, as appropriate, and Mann-Whitney test for numerical variables. Statistical significance will be considered as p < 0.05 for two-tailed tests. Results: Outof the 98 patients scheduled for treatment, 39 patients underwent at least 2 evaluations and had their exams analyzed. There was a 26% incidence of overall CT, with half of these patients by LVEF reduction criteria and, considering only patients with lung cancer, there was an incidence of 35% with CT. Dividing the total sample into CT and non-CT groups, a higher number of men, smokers and patients with lung cancer was observed, as well as a lower LVEF baseline (67% vs 62.50, p = 0.014) in the CT group. Concomitant chemotherapy or higher baseline coronary calcium scores did not appear to increase the risk of CT among patients, but the use of beta-blockers was restricted to patients who did not develop an event. There was a reduction in myocardial work parameters in the 2nd month assessment: global index (GWI) 1833 vs 2334, p = 0.006, constructive work (GCW) 2299 vs 2683, p = 0.040, and work efficiency (GWE) 83 vs 95, p = 0.025 and tendency towards increased myocardial work loss (GWW) 286 vs 116, p = 0.064, in the comparison between groups. Those who met CT criteria had a longer overall survival, as did those who developed other immune-mediated adverse events and metformin users. Conclusions: This was the first study that carried out cardiotoxicity surveillance in patients undergoing immunotherapy, with a surprising finding of events in a small but high-risk sample. The development of immune-mediated toxicities seems to be related with therapeutic response. Also, the use of metformin seems to contribute to this response, as already demonstrated in preclinical studies.