Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data.

e15100Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]