Among 6,925 patients receiving anti-PD-(L)1 therapies, ICI-related MACE occurred in 0.6%, with myocarditis accounting for 45% of events and often presenting with concurrent noncardiac irAEs (65%).
Observational (n=6,925)
Yes
What is the incidence and clinical presentation of major adverse cardiac events in patients receiving immune checkpoint inhibitors?
Immune checkpoint inhibitor-related major adverse cardiac events are rare (0.6%) but often severe, frequently presenting as myocarditis with concurrent noncardiac immune-related adverse events, highlighting the need for multidisciplinary awareness.
PURPOSE Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients. METHODS We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute–Cancer Therapy Evaluation Program for National Cancer Institute–sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti–programmed cell death protein-1 (anti–PD-1)/programmed cell death-ligand 1 (anti–PD-L1) alone or with additional anticancer therapies. RESULTS A total of 6,925 participants received anti–PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti–PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being ≥ grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti–PD-(L)1 + targeted therapies compared with anti–PD-(L)1 + anti–cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti–PD-(L)1-based combination therapies versus single-agent anti–PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis. CONCLUSION Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non–ICI-based anticancer therapies with anti–PD-(L)1 treatments is needed.
Naqash et al. (Sat,) conducted a observational in Cancer treated with immune checkpoint inhibitors (n=6,925). anti-PD-1/anti-PD-L1 therapies was evaluated on Incidence of ICI-related MACE. Among 6,925 patients receiving anti-PD-(L)1 therapies, ICI-related MACE occurred in 0.6%, with myocarditis accounting for 45% of events and often presenting with concurrent noncardiac irAEs (65%).