Dataset Information

A retrospective analysis of cardiovascular adverse events associated with immune checkpoint inhibitors.

ABSTRACT:

Background

Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several cancer types, the incidence of immune-related cardiovascular (CV) adverse events poses an additional health concern and has been reported.

Methods

We performed a retrospective analysis of the FDA Adverse Event Reporting System data of suspect product reports for immunotherapy and classical chemotherapy from January 2010-March 2020. We identified 90,740 total adverse event reports related to immune checkpoint inhibitors and classical chemotherapy.

Results

We found that myocarditis was significantly associated with patients receiving anti-program cell death protein 1 (PD-1) or anti-program death ligand 1 (PD-L1), odds ratio (OR) = 23.86 (95% confidence interval [CI] 11.76-48.42, (adjusted p-value) q < 0.001), and combination immunotherapy, OR = 7.29 (95% CI 1.03-51.89, q = 0.047). Heart failure was significantly associated in chemotherapy compared to PD-(L)1, OR = 0.50 (95% CI 0.37-0.69, q < 0.001), CTLA4, OR = 0.08 (95% CI 0.03-0.20, q < 0.001), and combination immunotherapy, OR = 0.25 (95% CI 0.13-0.48, q < 0.001). Additionally, we observe a sex-specificity towards males in cardiac adverse reports for arrhythmias, OR = 0.81 (95% CI 0.75-0.87, q < 0.001), coronary artery disease, 0.63 (95% CI 0.53-0.76, q < 0.001), myocardial infarction, OR = 0.60 (95% CI 0.53-0.67, q < 0.001), myocarditis, OR = 0.59 (95% CI 0.47-0.75, q < 0.001) and pericarditis, OR = 0.5 (95% CI 0.35-0.73, q < 0.001).

Conclusion

Our study provides the current risk estimates of cardiac adverse events in patients treated with immunotherapy compared to conventional chemotherapy. Understanding the clinical risk factors that predispose immunotherapy-treated cancer patients to often fatal CV adverse events will be crucial in Cardio-Oncology management.

SUBMITTER: Lal JC

PROVIDER: S-EPMC8161966 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Backgrounds: Immune checkpoint inhibitors (ICIs) are considered cornerstones of oncology treatment with durable anti-tumor efficacy, but the increasing use of ICIs is associated with the risk of developing immune-related adverse events (irAEs). Although ICI-associated pancreatic adverse events (AEs) have been reported in patients treated with ICIs, the clinical features and spectrum of pancreatic AEs are still not well-defined. Therefore, this study aimed to identify the association between pancreatic AEs and ICIs treatments and to characterize the main features of ICI-related pancreatic injury (ICIPI) based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsData from the first quarter of 2015 to the first quarter of 2021 in the database were extracted to conduct a disproportionality analysis. The selection of AEs related to the pancreas relied on previous studies and preferred terms from the Medical Dictionary for Regulatory Activities. Two main disproportionality analyses-the reporting odds ratio (ROR) and information component (IC)-were used to evaluate potential associations between ICIs and pancreatic AEs.ResultsIn total, 2,364 cases of pancreatic AEs in response to ICIs were extracted from the FAERS database, of which, 647 were identified as ICI-associated pancreatitis and 1,293 were identified as ICI-associated diabetes mellitus. Generally, significant signals can be detected between pancreatic AEs and all ICIs treatments (ROR025 = 3.30, IC025 = 1.71). For monotherapy, the strongest signal associated with pancreatitis was reported for anti-PD-L1 (ROR025 = 1.75, IC025 = 0.76), whereas that with diabetes mellitus was reported for anti-PD-1 (ROR025 = 6.39, IC025 = 2.66). Compared with monotherapy, combination therapy showed stronger associations with both ICI-associated pancreatitis (ROR025 = 2.35, IC025 = 1.20 vs. ROR025 = 1.52, IC025 = 0.59) and ICI-associated diabetes mellitus (ROR025 = 9.53, IC025 = 3.23 vs. ROR025 = 5.63, IC025 = 2.48), but lower fatality proportion.ConclusionsICIs were significantly associated with the over-reporting frequency of pancreatic AEs, in which combination therapy posed a higher reporting frequency. Therefore, patients should be informed of these potential toxicities before ICIs medications are administered.

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