A systematic review and meta-analysis published in JAMA Network Open reveals a low rate of cardiovascular adverse events (CVAEs) and myocarditis in patients treated with immune checkpoint inhibitors (ICIs). The study, encompassing 83,315 patients from 589 trials, underscores the importance of monitoring and management strategies for these potential complications.
Incidence of CVAEs and Myocarditis
The meta-analysis indicated that the incidence of CVAEs induced by anti-programmed cell death 1 (PD-1) and/or programmed cell death ligand 1 (PD-L1) inhibitors was 0.80% (95% CI, 0%-1.66%). Notably, cemiplimab was associated with a higher risk for CVAEs compared to other compounds. The incidence of CVAEs after treatment with ipilimumab was 1.07% (95% CI, 0%-2.58%).
While the incidence of myocarditis was significantly higher after treatment with dual ICIs, the incidence of CVAEs was not higher with ICI combination with chemotherapy, dual ICIs, or tyrosine kinase inhibitors. This suggests that specific combinations may elevate the risk of myocarditis, warranting careful consideration in treatment planning.
Management and Mortality
The study highlighted a significant gap in evidence-based monitoring and treatment strategies for myocarditis induced by ICIs. Mortality associated with myocarditis was observed in 83 of 220 patients (37.7%). Prospective data from 40 patients with myocarditis suggested that systematic screening for respiratory muscle involvement, active ventilation, prompt use of abatacept, and the addition of ruxolitinib may decrease mortality rates related to myocarditis.
Study Details and Limitations
The researchers conducted two separate analyses: one focusing on phase 1 to 4 trials involving adults with malignant neoplasms treated with ICIs, and another including retrospective analyses and case reports on the clinical manifestations and treatment of ICI-induced CVAEs. The primary outcome was the incidence of CVAEs in clinical trials with ICIs and ICI combination therapies. For the second study, the focus was on evidence supporting specific management strategies to potentially decrease the mortality rate of myocarditis.
Limitations of the study include the lack of individual patient-level meta-analyses and the reliance on treatment-related adverse event reporting, which limited the examination of cardiac parameters.
Expert Commentary
"Early recognition, ICI therapy cessation, prompt initiation of corticosteroid therapy, and escalation of therapy are all crucial elements for achieving optimal outcomes," the study authors emphasized. They also noted the absence of established monitoring strategies and the reliance on anecdotal evidence for treating corticosteroid-refractory ICI-induced myocarditis, calling for prospective clinical trials and treatment registries.
