Evaluating risk factors, biomarkers and management of myocarditis following treatment with checkpoint inhibitors. A retrospective analysis

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Abstract Immunotherapy is an exciting treatment of many malignancies. They upregulate the immune system to attack cancerous cells. Immune checkpoint inhibitor (ICIs) are among armamentarium of immunotherapy agents that target immune system negative regulation and are known to induce myocarditis [1]. This is a rare but increasingly recognised complication as immunotherapy regimens become more widely used as first line therapy for a range of tumour types. Due to its infrequent presentation, there remains uncertainty regarding its diagnosis and management [2]. We conducted a single centre retrospective analysis of patients undergoing immunotherapy at a cancer centre in United Kingdom. The cases were referred to the regional cardio-oncology service for suspected myocarditis. In this single center retrospective analysis, data of 60 patients with suspected myocarditis (based on symptoms, cardiac biomarkers or ECG) presenting over a 2 year period were evaluated. Of those 25 (42%) developed MRI-proven myocarditis with mean period to toxicity post treatment of 99.5 days. In the same time period 1027 patients experienced all-type immunotherapy related adverse events (irAEs) thus myocarditis accounted for 2.4% of all ICI-induced toxicity. 35% had significant pre-existing cardiac history including ischaemic heart disease, valvular disease and ventricular impairment. Patients with myocarditis had average peak troponin of 276 and average peak pro-BNP of 2,265. Less than 10% of patients with myocarditis had pre-existing autoimmune diagnosis (rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease). Average maximum grade toxicity was 3. The majority of patients were managed with steroids with 48% receiving intravenous methylprednisolone followed by oral prednisolone and 28% patients receiving only oral steroids. 44% of patients also required steroid sparing agents such as tacrolimus or mycophenalate mofetil. Steroid tapering was adjusted based on the patient's symptoms with 32% of patients needing dose escalation for a flare. No patients restarted immunotherapy once myocarditis had been identified and overall survival remained comparable to those without myocarditis. In conclusion, myocarditis is a late complication of ICIs with higher incidence among patients with significant cardiac history. Associated biomarkers are significantly elevated and correlate well with the presence of myocarditis. Steroids remain the mainstay of treatment for those who develop myocarditis secondary to immunotherapy but there is also an important role for other agents such as tacrolimus or mycophenalate mofetil. Funding Acknowledgement Type of funding sources: None.

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