In a study presented at the 2022 ASCO Annual Meeting (Abstract 2508) and simultaneously reported in the Journal of Clinical Oncology, Naqash et al identified the incidence of major adverse cardiac events among patients receiving immune checkpoint inhibitors for cancer as captured in the serious adverse events reporting database of the National Cancer Institute (NCI)–Cancer Therapy Evaluation Program.
Study Details
The retrospective pooled analysis included patients treated with anti–PD-1/anti–PD-L1 (anti–PD-(L)1) agents alone or in combination with other agents in NCI-sponsored clinical trials between June 2015 and December 2019.
Key Findings
Among 6,925 patients included in the analysis, 3,354 (48%) received single-agent anti–PD-(L)1 therapy. A total of 3,571 patients received anti–PD-(L)1-based combinations, including combination with anti–CTLA-4 treatment in 26%, other immunotherapies in 2%, targeted therapies in 3%, and chemotherapy in 5%.
Among the 6,925 patients, immune checkpoint inhibitor–related major adverse cardiac events occurred in 40 patients (0.6%); of these, 31 (77.5%) were grade ≥ 3. Major adverse cardiac events consisted of myocarditis in 18 patients (45%), followed by acute coronary syndromes in 8, dysrhythmias in 6, cardiomyopathy in 5, pericardial disorders in 2, and cardiac arrest in 1.
Concurrent multisystem involvement with other noncardiac immune-related adverse events was observed in 26 patients (65%), with one or more concurrent noncardiac adverse event observed in 15 patients (83%) with myocarditis. Concurrent myositis and transaminitis was observed in 7 of the 40 patients.
The incidence of major adverse cardiac events was 0.47% (16 of 3,354 patients) with single-agent anti–PD-(L)1 treatment; incidence rates were 0.90% (16 of 1,767) in combination with anti–CTLA-4 treatment, 2.1% (5 of 235) in combination with targeted therapies, and 0.83% (5 of 362) in combination with chemotherapy. The incidence of myocarditis was 0.36% with combination therapy vs 0.15% with single-agent anti–PD-(L)1 treatment (P = .08).
A total of 37 patients with major adverse cardiac events (93%) were hospitalized, with 12 admitted to the intensive care unit. Among the 37 hospitalized patients, 17 had myocarditis.
Death occurred in 4 (22.5%) of the 18 patients with myocarditis. All four patients who died had concurrent myositis.
The investigators concluded, “Increasing patient and prescriber awareness in understanding patterns of immune checkpoint inhibitor[–associated] major adverse cardiac events and associated noncardiac immune-related adverse events should be emphasized. Better characterization of the risk of major adverse cardiac events with the concurrent use of non–immune checkpoint inhibitor–based anticancer therapies with anti–PD-(L)1 treatments is needed.”
Elad Sharon, MD, MPH, of the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
