{
  "abstract": "Introduction Immune checkpoint inhibitor (ICI) related myocarditis (ICIRM) is the commonest and most serious of ICI induced cardiotoxicities. Its rarity, severity and complexity hinder a consensus on treatment guidelines. We conducted a systematic review (SR) of real-world evidence aiming to formulate the most effective treatment approach for ICIRM.Methodology 5 databases (MEDLINE, Embase, Cochrane, Scopus, Google Scholar) were searched for ‘immune checkpoint inhibitors’ and ‘myocarditis’. Only real-world studies were included. Baseline demographics, myocarditis diagnoses, disease characteristics, treatments, and outcomes were extracted by atleast 2 independent reviewers.Results A pooled analysis of 588 patients from 17 studies was done. Most common primary tumours were melanoma (n=62) and non-small cell lung cancer (n=51). PD-1 inhibitors (n=208) were the commonest monotherapy, followed by CTLA-4 (n=14) and PD-L1 (n=11) inhibitors. Combination therapy wise, PD-1/CTLA-4 (n=20) superseded PD-L1/CTLA-4 (n=2) inhibitors.ICIRM was diagnosed using composite criteria in 8/17 studies (clinical, ECG, troponin, cardiac MRI) with 9/17 incorporating histology (endomyocardial biopsy).Methylprednisolone (MP) was first line (1L) (17/17 studies), with evidence of combination intravenous immunoglobulin (IVIG) (8/17) more commonly than plasmapheresis (2/17). Differential dosage was identified in 8/17, whereas dose ranges in 3/17. 2/17 advocated1g intravenous MP (table 1). Lower mortality and incidence of major adverse cardiovascular event (MACE) were linked to higher steroid dose (3/17 and 3/17 studies respectively) and earlier initiation of steroids i.e., within <24 h after presentation (1/17 and 1/17 respectively).In the steroid refractory state, IVIG (4/17), anti-thymocyte globulin (ATG) (2/17) and plasmapheresis (1/17) were used only as 1L; tocilizumab in 1L (1/17), 2L (2/17) and 3L settings (1/17); tacrolimus, mycophenolate mofetil (MMF), abatacept, infliximab in 1L or 2L setting without any evidence of comparative benefit over each other or consensus over treatment sequencing.ICIs were subject to immediate cessation (9/17) except 1/17 which involved continuation if mild ICIRM. 2/17 considered ICI rechallenge, 1/17 in mild disease and 1/17 in 8 to 12 months.Biomarker surveillance utilised troponin I (7/17) more commonly than troponin T (5/17).Conclusion We reviewed 17 studies to identify a consensus on treatment strategies for ICIRM along with treatment-related factors promoting survival prognostication, including timing of steroid commencement and cessation of ICIs. Analysis is limited by the lack of individual patient data. We provide suggestions for future research regarding steroid usage characteristics, combination therapies, immunosuppressant treatment sequencing and comparative analysis if refractory disease.Abstract 1-018 Table 1This table demonstrates details of steroid therapy in ICI related Myocarditis extracted from our selected studies Study (Author Year) Number treated with steroids Dose strategy Dose When was treatment started Duration of treatment Whether there was a taper Cadour 202233Single dose1gWithin first 3 days of admissionNot reportedNoHe 202313Differential dose0.5 mg/kg/d (mild), 1–2 mg/kg/d (severe), 1g/d (fulminant)1 day (median)3–5 daysNoMahmood 201831Range of doses0–1000 mg (did not specify lowest non-zero dose); 120 mg (median)21.4 h (mean)Not reportedNoLei 202218Single dose1–2 mg/kgNot reported3–5 daysYesLiu 202138Differential dose<60 mg/d (low dose), 60–300 mg/d (intermediate dose), 301–500 mg/d (high dose)1–3 days (median)Not reportedNoCautela 202054Not reported 1 day (median) Salem 202336Dose strategy 1: Q1Dose strategy 2: Q2≥500 mg/day (in 90% of Q1) in the beginning and then 155 mg/day (mean in first month);96 mg/day (mean in first month)2 days; not reported≥2 days (mean); not reportedYesZhang 2020126Differential dose (not based on severity but assigned retrospectively)<60 mg/day, 60–500 mg/day, 501–1000 mg/day<24 h, 24–72 h, >72 hNot reportedNoXie, 202043Differential dose (not based on severity but assigned retrospectively)<500 mg/day, >500 mg/day<24, >24 hNot reportedNoFurukawa 20234Not reportedNot reportedNot reportedNot reportedNoXiao 20237Range of doses1 mg/kg to 4 mg/kg, or 500–100 mg/day 9 weeks (median)? should be yes given the extensive duration but not explicitly saidAldrich 202135Range of doses0.1–18 mg/kg/dayNot reported45 days (median)? should be yes given the extensive duration but not explicitly saidThavendiranathan63Differential dose<60 mg/day, 60–500 mg/day, 501–1000 mg/day<24 h, 24–72 h, >72 hNot reportedNoPuzanov 202113Single dose1g methylprednisolone7.5 days (median)3–5 days of IVYesZhuang, 202345Differential doseMilder: 1–2 mg/kg/day; more severe: 500–1000 mg/day -> 1–2 mg/kg/dayNot reported3–7 days; 3–5 daysYesBoughdad 202110Not reportedNot reportedNot reportedNot reportedNoMoreira 201910Not reportedNot reportedNot reportedNot reportedNo",
  "authors": [
    {
      "affiliations": [
        "Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK",
        "Both Authors contributed equally"
      ],
      "name": "Ishikaa Mukherjee"
    },
    {
      "affiliations": [
        "School of Clinical Medicine, University of Cambridge, Cambridge, UK",
        "Both Authors contributed equally"
      ],
      "name": "Justine Tin Nok Chan"
    },
    {
      "affiliations": [
        "Cardio Oncology Service, Barts Health NHS Trust, London, UK"
      ],
      "name": "Aruni Ghose"
    },
    {
      "affiliations": [
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Sabrina Taylor"
    },
    {
      "affiliations": [
        "University College London Medical School, London, UK"
      ],
      "name": "Abhinav Kandala"
    },
    {
      "affiliations": [
        "School of Clinical Medicine, University of Cambridge, Cambridge, UK"
      ],
      "name": "Arefin Haque"
    },
    {
      "affiliations": [
        "Cardio Oncology Service, University College London Hospitals NHS Foundation Trust, London, UK"
      ],
      "name": "Carl Simela"
    },
    {
      "affiliations": [
        "Southeast Wales Immunotherapy Toxicity Service, Velindre Cancer Centre, Velindre, University NHS Trust, Cardiff, UK"
      ],
      "name": "Ricky Frazer"
    },
    {
      "affiliations": [
        "Cardio Oncology Service, Barts Health NHS Trust, London, UK",
        "University College London Medical School, London, UK",
        "University College London Institute of Cardiovascular Science, London, UK"
      ],
      "name": "Charlotte Manisty"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, UK"
      ],
      "name": "Akash Maniam"
    },
    {
      "affiliations": [
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
        "Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK"
      ],
      "name": "Brent O’Carrigan"
    },
    {
      "affiliations": [
        "Cardio Oncology Service, Barts Health NHS Trust, London, UK",
        "University College London Medical School, London, UK",
        "University College London Institute of Cardiovascular Science, London, UK"
      ],
      "name": "Arjun Kumar Ghosh"
    }
  ],
  "title": "1-018 Immune checkpoint inhibitor related myocarditis: a systematic review to map the most effective treatment approach",
  "uid": "f9bcf22c-cd62-591c-9b02-a9471149988d"
}