Safety of immune checkpoint inhibitor rechallenge and mid-term outcomes after suspected cardiovascular immune-related adverse events

Background Current European Society of cardiology guidelines recommend systematic troponin screening to detect potential cardiovascular (CV) immune-related adverse events (irAEs) in the increasing numbers of cancer patients receiving immune-checkpoint inhibitors (ICIs), increasing the number of patients referred and broadening the severity spectrum of CV irAEs. Management and outcomes in patients with suspected CV irAEs, are poorly defined. The safety of ICI rechallenge, particularly in patients fulfilling contemporary ICI-myocarditis diagnostic criteria, remains uncertain. Methods Prospective single-centre cohort including consecutive adults referred for suspected CV irAEs. Objectives were to describe outcomes after initial assessment, identify predictors of mid-term CV events, and evaluate outcomes of ICI rechallenge in patients with and without initial CV irAEs. Results Among 175 patients (median age 61 years [IQR 48–72]; 77.1% women), 95 (54.3%) had adjudicated CV irAEs at referral, including 72 (41.1%) fulfilling diagnostic criteria for non-severe ICI-myocarditis. During 234 ± 154 days of follow-up, 15 patients died (12 cancer-related, 1 CV, 2 other). Predictors of CV events included significant coronary stenosis (HR 4.77; 95% CI 1.39–16.40; P = 0.013), hospital admission (HR 13.21; 95% CI 2.51–69.52; P = 0.0023), ICI rechallenge (HR 9.30; 95% CI 1.77–48.77; P = 0.0084), and positive Lake Louise cardiac magnetic resonance (CMR) (HR 18.84; 95% CI 5.13–69.20; P < 0.0001). Eighty-four patients (48.0%) were rechallenged; 3 (3.6%) developed non-severe myocarditis, with no ICU admissions or CV deaths. Ten out of 53 (18.87%) patients without initial CV irAEs who continued ICIs developed CV events.