Immune Checkpoint Inhibitor–Induced Myocarditis: Contemporary Retrospective Analysis

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In a retrospective cohort study of 160 patients with cancer who were suspected of having immune checkpoint inhibitor (ICI)-induced myocarditis, published in JACC: CardioOncology, Osnat Itzhaki Ben Zadok, MD, MSc, and colleagues found that severe ICI-induced myocarditis seemed to be linked to increased 1-year cardiovascular mortality, which they noted was “lower than previously reported.” As for patients with nonsevere ICI-induced myocarditis, they had similar outcomes as those who did not have this cardiovascular side effect.

As stated by the investigators: “With the ever-expanding use of ICI agents for treating both solid and hematologic malignancies and the rapid evolution of therapeutic options for ICI myocarditis, it is imperative to reevaluate the long-term cardio-oncologic management of patients with ICI myocarditis.”

Study Details

Between January 2015 and June 2022, 10,046 patients diagnosed with cancer received ICI therapy at Massachusetts General Brigham Health System. The focus of this study was the 160 patients who were suspected of having ICI-induced myocarditis. In addition to 1-year cardiovascular mortality, all-cause mortality, and cardiovascular readmissions, the study authors also evaluated 1-year resumption of immune checkpoint inhibitors and left ventricular ejection fraction (LVEF) over a median follow-up of 18 weeks.

Patients included in the analysis had received at least one of the following ICIs: pembrolizumab, nivolumab, durvalumab, ipilimumab, cemiplimab-rwlc, avelumab, and/or atezolizumab. In addition, these patients had evidence of an abnormal troponin level or had undergone cardiac magnetic resonance imaging. Clinical, laboratory, imaging, and histopathology data were reviewed. A total of 28 patients were considered to have severe ICI-induced myocarditis; 96, nonsevere ICI-induced myocarditis; and 36, negative cases. These classifications were based on the International Cardio-Oncology Society criteria.

The median patient age was 72. Malignant melanoma (28%), renal cell carcinoma (25%), and lung cancer (19%) were the most prevalent underlying cancer types. Between those with positive and negative ICI-induced myocarditis, baseline cardiovascular comorbidities were comparable, except for a higher prevalence of a history of atrial fibrillation in positive patients (27% vs 8%; P = .023).

Key Findings

First, the study’s findings shed light on the clinical presentation of patients with severe vs nonsevere ICI-induced myocarditis. Those with severe myocarditis were found to have presented earlier and after fewer doses of an ICI than those with nonsevere myocarditis. Patients with severe ICI-induced myocarditis seemed to have a higher numerical rate of diplopia and/or ptosis than did those with nonsevere myocarditis (36% vs 18%; P = .077), although most of the clinical symptoms were similar between the two groups. In addition, levels of N-terminal brain natriuretic peptide were numerically higher in patients with than in those without severe myocarditis. Also, patients with severe ICI-induced myocarditis appeared to be more likely to be treated with intravenous steroids (96% vs 53%, P = .007).

Turning to long-term outcomes, the investigators discovered an increased risk of 1-year cardiovascular mortality in patients with severe myocarditis compared with those who had nonsevere myocarditis (29% vs 5%; hazard ratio = 6.52; 95% confidence interval = 2.2–19.6; P < .001). The cardiovascular mortality rate was found to be similar in those with nonsevere myocarditis and in those with negative cases. Across all three groups (severe, nonsevere, negative), the 1-year all-cause mortality did not seem to differ (P = .74); the rates of 1-year cardiovascular readmission as well as long-term LVEF were similar across all three groups as well. Finally, even in negative cases, resumption of treatment with ICIs was low.

The investigators concluded, “With increasing use of ICI agents and greater awareness about immune-related adverse events, there is an expected increase in the identification of nonsevere and subclinical cases of ICI myocarditis. Future research efforts should focus on the risk stratification of patients with ICI myocarditis in an effort to identify those patients who may tolerate resumption of ICI therapy to improve cancer outcomes, without increasing adverse cardiovascular events.”

Dr. Zadok, of the Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, was the corresponding author of the JACC: CardioOncology article.

Disclosure: For full disclosures of the study authors, visit

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