Rate of Cardiovascular Adverse Events, Myocarditis May Be Low in Trials Assessing ICIs

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Even with a low rates of cardiovascular adverse events in patients treated with immune checkpoint inhibitors, cancer care teams should still focus on multidisciplinary approaches and early recognition of these events.

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Rate of Cardiovascular Adverse Events, Myocarditis May Be Low in Trials Assessing ICIs

The rate of cardiovascular adverse events (CVAEs) and/or myocarditis in patients treated with immune checkpoint inhibitors (ICIs) was low, as demonstrated in a systematic review and meta-analysis, although the need persists for monitoring and management strategies, according to findings published in JAMA Network Open.

“Early recognition, ICI therapy cessation, prompt initiation of corticosteroid therapy, and escalation of therapy are all crucial elements for achieving optimal outcomes,” study authors wrote.

Among 83,315 patients from 589 trials, the incidence of CVAEs induced by anti-programmed cell death 1 and/or programmed cell death ligand 1 was 0.80% (95% CI, 0%-1.66%). There were no differences between the different compounds except for cemiplimab (Libtayo), which was linked with a higher risk for CVAEs. After treatment with ipilimumab (Yervoy), the incidence of CVAEs was 1.07% (95% CI, 0%-2.58%).

After treatment with dual ICIs, the incidence of myocarditis was significantly higher; however, the incidence of CVAEs was not higher with ICI combination with chemotherapy, dual ICIs, or tyrosine kinase inhibitors.

Researchers also noted that evidence from the trials in this meta-analysis was lacking regarding recommended monitoring and treatment strategies for myocarditis from ICIs.

Mortality associated with myocarditis was observed in 83 of 220 (37.7%) patients. Researchers analyzed prospective data from 40 patients with myocarditis, which indicated that systematic screening for respiratory muscle involvement, in addition to active ventilation, prompt use of abatacept (Orencia), and the addition of ruxolitinib (Jakafi), may decrease mortality rates related to myocarditis.

In this systematic review and meta-analysis, researchers performed 2 separate analyses. The first study consisted of phase 1 to 4 trials including adults with malignant neoplasms who were treated with an ICI and had available data on toxicity and/or ICI-related death. The second study included retrospective analyses and case reports about the clinical manifestations and treatment of patients with ICI-induced CVAEs. Sources used during these analyses included articles published through April 2023. Case reports, letters, reviews, retrospective analyses, editorials, and studies with dose escalation or fewer than 11 patients in each group were excluded from the first study. Studies that were not published in English were excluded from the second study.

The primary outcome of study 1 was the incidence of CVAEs in clinical trials with ICIs and ICI combination therapies. For study 2, researchers focused on evidence that supported specific management strategies to potentially decrease the mortality rate of myocarditis.

There are several limitations to this study, including a lack of individual patient level meta-analyses. In addition, most studies in this analysis reported on treatment-related adverse events and/or immune-related adverse events, which limited the examination of cardiac parameters.

“To our knowledge, there are no evidence-based established monitoring strategies,” the study authors wrote. “The treatment of ICI-induced myocarditis in corticosteroid-refractory disease is based on anecdotal evidence. Prospective clinical trials or prospective registrations of treatments and outcomes are therefore warranted.”

Reference

Nielsen DL, Juhl CB, Nielsen OH, Chen IM, Herrmann J. Immune Checkpoint Inhibitor-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis. JAMA Oncol. Published online August 22, 2024. doi:10.1001/jamaoncol.2024.3065

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