Immune Checkpoint Inhibitors—Associated Cardiotoxicity

Abstract

Large population-based studies examining differences in ICI-associated cardiotoxicity across cancer types and agents are limited. Data of 5518 cancer patients who received at least one cycle of ICIs were extracted from a large network of health care organizations. ICI treatment groups were classified by the first ICI agent(s) (ipilimumab, nivolumab, pembrolizumab, cemiplimab, avelumab, atezolizumab, or durvalumab) or its class (PD-1 inhibitors, PD-L1 inhibitors, CTLA4-inhibitors, or their combination (ipilimumab + nivolumab)). Time to first cardiac adverse event (CAE) (arrhythmia, acute myocardial infarction, myocarditis, cardiomyopathy, or pericarditis) developed within one year after ICI initiation was analyzed using a competing-risks regression model adjusting for ICI treatment groups, patient demographic and clinical characteristics, and cancer sites. By month 12, 12.5% developed cardiotoxicity. The most common cardiotoxicity was arrhythmia (9.3%) and 2.1% developed myocarditis. After adjusting for patient characteristics and cancer sites, patients who initiated on monotherapy with ipilimumab (adjusted Hazard Ratio (aHR): 2.00; 95% CI: 1.49–2.70; p < 0.001) or pembrolizumab (aHR: 1.21; 95% CI: 1.01–1.46; p = 0.040) had a higher risk of developing CAEs within one year compared to nivolumab monotherapy. Ipilimumab and pembrolizumab use may increase the risk of cardiotoxicity compared to other agents. Avelumab also estimated a highly elevated risk (aHR: 1.92; 95% CI: 0.85–4.34; p = 0.117) compared to nivolumab and other PD-L1 agents, although the estimate did not reach statistical significance, warranting future studies.

Cardiovascular adverse events induced by immune checkpoint inhibitors: A real world study from 2018 to 2022

“…A large population-based study from multiple medical institutions showed that patients with CAEs had a higher burden of comorbidities than patients who did not develop CAEs within 1 year of ICIs initiation ( P = 0.0042). Patients who developed CAEs were more likely to have cerebrovascular disease (12.9% vs. 10.3%, P = 0.0375), congestive heart failure (5.9% vs. 2.6%, P < 0.001), myocardial infarction (4.8% vs. 2.3%, P = 0.0002), peripheral vascular disease (15.6% vs. 12.3%, P = 0.0129), hypertension (50.8% vs. 45.1%, P = 0.0046), or renal disease (13.7% vs. 10.8%, P = 0.0221) ( 7 ). In addition, an international registry identified combination therapy, diabetes, obesity, and anti-CTLA-4 therapy were independent risk factors for cardiotoxicity ( 10 ).…”

“…Data from a large network of healthcare organizations showed that of 5,518 cancer patients treated with at least one ICI cycle, 691 (12.5%) developed cardiotoxicity. The most common cardiotoxicity was arrhythmia (9.3%), and 2.1% of the patients developed myocarditis at 12 months ( 7 ). In this real-world study, we found that the incidence rate of CAE in patients who received at least four cycles of ICI within 1 year was 12.93%.…”

Response to immunotherapy in a patient with advanced epithelioid sarcoma of adrenal gland: A case report

“…ICI-associated cardiotoxicity is a rare occurrence that may be fatal. Although data from a large population-based epidemiology study indicated no difference between PD-1 and PD-L1 inhibitors in terms of risk of cardiotoxicity, patients initiated on pembrolizumab were vulnerable to developing cardiotoxicity ( 24 ).…”

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma

“…The ICI related myocarditis is generally considered highly arrhythmogenic and fatal; however, the exact pathogenesis is still poorly recognized and understood ( 12 , 13 ). Myocarditis caused by ICIs represents <1% of immune-related adverse events.…”