Abstract 4369783: Clinical Safety Outcomes of ICI Rechallenge following ICI-myocarditis and other Cardiotoxicities

Abstract

Background: Cardiotoxicity is a major limitation to the effective use of immune checkpoint inhibitor (ICI) therapies. In non-cardiac models, rechallenge with ICI-therapy after non-life threatening toxicity is generally tolerable and effective. Yet, whether this is seen among patients with cardiovascular toxicities following ICI-treatment is unknown. Aims: Assess the safety and efficacy of ICI-rechallenge (restart) among patients with serious cardiovascular events following immunotherapy initiation. Methods: Leveraging a large comprehensive cancer center cohort of consecutive cancer patients treated with ICI-therapies between 2014 - 2021, we identified all patients rechallenged with ICI-therapy following a major cardiovascular event. The primary outcome was development or recurrence of a major adverse cardiac event (MACE), defined as possible or definite ICI-related myocarditis, heart failure, atrial fibrillation, and other symptomatic atrial or ventricular arrhythmias by 12 months post-rechallenge, as defined by standard cancer and cardiovascular definitions. Safety outcomes, including overall survival by ICI-rechallenge status, were compared. Results: Overall, among 5,173 ICI-treated patients, 40 rechallenged patients (mean age 69 ± 8.8 years, 45.0% female, 2.5% prior myocardial-infarction, BMI 28.9 kg/m2, 92.7% on PD-1 therapy, and 12.5% index-ICI myocarditis) with cardiotoxicity on ICI-therapy were identified. Mean left ventricular ejection fraction (LVEF) at toxicity diagnosis was 49.6%; and 17.5% had a concurrent non-cardiac ICI-related toxicity. Steroids were acutely used in 20.0%, and 87.5% received at least one immunosuppressive or cardiovascular therapy. Mean time from toxicity to ICI-therapy rechallenge was 15.8 days. In follow-up, 20.5% experienced a recurrent or additional MACE, including 40% of those with ICI-myocarditis; those with ESRD saw higher recurrence rates ( P <0.05). Among those with available serial imaging, there was no difference in LVEF (49.6% vs. 50.4%, P =0.843). Over a median follow-up of 21 months, ICI-rechallenged patients saw longer overall survival (median survival 459 vs. 293 days, P =0.055). Conclusions: In this cohort, ICI-rechallenge following cardiac events appears to associate with modest risk of adverse events, but improved survival.