Background:
Immune checkpoint inhibitors (ICIs), including programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitors, are increasingly used in treatment of advanced stage cancers due to a well-established mortality benefit. ICI therapy is associated with immune mediated toxicity which may impact any organ system. Cardiovascular toxicities are rare based on existing data, but associated with high mortality rates.
Objectives:
The aim of this study is to determine whether preexisting cardiac conditions and/or cardiac therapies are associated with an increased or decreased risk of developing cardiotoxicity after ICI exposure.
Methods:
All patients treated with ICI therapy from March 2011 through October 2019 at our institution were identified. Demographic information, treatment dates, pre-treatment cardiac conditions and comorbidities, cancer types, pre-treatment cardiac biomarkers, and pre-treatment cardio-protective medication use were determined for each patient. New cardiac diagnoses after ICI exposure were identified in the medical record. Multivariate logistic regression was used determine the association between preexisting cardiac conditions and/or cardiac therapies and the development of cardiotoxicity after ICI exposure.
Results:
There were 902 patients identified with 1071 ICI exposures. The majority of exposures were to a PD-1 inhibitor (70%), with the most common drugs being pembrolizumab (42.8%) and nivolumab (26.5%). Eighty-nine new cardiac diagnoses were coded after initiation of ICI therapy. Sixteen events occurred within 30 days of initial exposure to an ICI and likely represent new cases of immune checkpoint inhibitor associated cardiotoxicity (incidence 1.5%). Of these events, one was confirmed as myocarditis, seven were heart failure without confirmation of myocarditis, three were arrhythmia, one was pericarditis, three were myocardial infarction and one was ventricular tachyarrhythmia/sudden cardiac death, without confirmed myocarditis or heart failure. There was an additional case of myocarditis identified within 90 days of initial exposure to ICI therapy, and a third case identified 115 days following exposure. All three patients who developed myocarditis died, consistent with the known high mortality rate of ICI associated myocarditis. One of the patients who developed myocarditis received pembrolizumab, one nivolumab and one cemiplimab (all PD-1 inhibitors). A history of heart failure increased the odds of developing a cardiac toxicity by 2.3 fold (95% CI 1.4 to 3.3, p<0.001) and prior beta-blocker exposure decreased the odds by 1.8 fold (95% -2.9 to -0.7, p=0.002).
Conclusion:
A history of heart failure is associated with an increased odds of developing cardiotoxicity after ICI exposure while prior beta blocker exposure appears to be protective.
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