Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved survival in patients with different cancer entities. It is estimated that nearly half of the patients with cancer will be eligible for immunotherapy in the near future. Cancer therapy-related cardiovascular toxicity (CTR-CVT) under ICI therapy could significantly increase morbidity and mortality. However, the real incidence and impact on survival of CTR-CVT are incompletely described.

Aim: To determine the incidence of CTR-CVT in patients with cancer under ICI therapy from the EcoR database of patients evaluated in our local Cardio-Oncology Unit according to the International Society of Cardio-Oncology (IC-OS) definitions.  

Results: The study cohort included 353 patients under ICI therapy (38% female, 63 ± 13 years, 72.5% metastatic cancer), 74.2% patients with malignant melanoma, 7.1% with non-small cell lung cancer, 6.5% with squamous cell carcinoma, 5.4% with Merkel cell carcinoma, 3.4% with hepatic carcinoma, 1.1% with oropharynx carcinoma and 2.4% with other cancer entities. The incidence of preexistent cardiovascular disease in this cohort was 27.2%. PD-1 inhibitors were the therapy of choice for 93.8% of patients, CTLA-4 inhibitors for 43.1% of patients and PD-L1 inhibitors for 10.2% of patients. According to the IC-OS definitions of CTR-CVT there were 68 cases (62 mild, 4 moderate and 2 severe) of cancer therapy related cardiac dysfunction (CTRCD), 11 cases of myocarditis, 38 cases of vascular toxicity, 14 cases of arterial hypertension and 62 cases of arrhythmias or QTc prolongation (Figure 1).

Patients with severe CTRCD (p < 0.001), myocarditis (p < 0.001), and arrhythmias or QTc prolongation (p = 0.013) showed an increased mortality rate at 24 months follow-up. All grade CTRCD (p = 0.153), vascular toxicity (p = 0.069) and arterial hypertension (p = 0.680) showed no impact on the 24 months survival rate.

Conclusion: Patients with cancer under ICI therapy showed increased mortality rates when developing severe CTRCD, myocarditis and arrhythmias or QTc prolongation. Further studies should define predictors of CTR-CVT, in order to improve cardio-oncology care in this cancer population.