In a meta-analysis reported in JAMA Oncology, Nielsen et al estimated the risk of cardiotoxicity associated with immune checkpoint inhibitor (ICI) treatment of cancers.
Study Details
The meta-analysis included 83,315 unique patients in 589 unique trials of ICIs and ICI combination therapies. The primary outcome of interest was the incidence of ICI-induced cardiovascular adverse effects (CVAEs).
Key Findings
The incidence of any-grade CVAEs related to anti–PD-1/PD-L1 treatment was 0.80% (95% confidence interval [CI] = 0%–1.66%), with an incidence of 1.07% with PD-1 inhibitors and 0.63% with PD-L1 inhibitors. The incidence of CVAEs associated with ipilimumab treatment was 1.07% (95% CI = 0%–2.58%). The highest incidence of myocarditis (0.97%) was associated with dual ICI therapy.
A separate analysis showed that myocarditis-related mortality occurred in 83 of 230 patients (37.7%) with treatment-related myocarditis. Prospective data from 40 patients with myocarditis suggested that systematic screening for respiratory muscle involvement, coupled with active ventilation, prompt use of abatacept, and addition of ruxolitinib, may decrease the associated mortality rate.
Summary
The investigators concluded: “Immune checkpoint inhibitor–induced CVAEs and/or myocarditis were recorded in 1.07% of patients in clinical trials. The CVAE mortality risk remains high, justifying the need for monitoring and management strategies for which evidence from randomized clinical trials is absent. Early recognition, ICI therapy cessation, prompt initiation of corticosteroid therapy, and escalation of therapy are all crucial elements for achieving optimal outcomes. Prospective clinical trials or at least prospective registration of treatments and outcomes are highly warranted.”
Dorte Lisbet Nielsen, MD, DMSc, of Herlev and Gentofte Hospital, University of Copenhagen, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
