Abstract
Immune checkpoint inhibitors (ICI) therapy is a breakthrough in the oncology field. By restoring antitumour T cell responses, ICI can induce frequent immune-related adverse events (irAE) with different tropisms depending on the therapeutic targets (Programmed cell Death 1 (PD-1), PD-ligand 1 (PD-L1) or Cytotoxic T Lymphocyte-Associated Protein 4 (CTLA-4)). The overall associated mortality is less than 2%, but some toxicities are associated with a poor outcome like myocarditis. ICI-associated myositis was initially reported as a rare irAE with an incidence of <1%. However, with the width use of ICI, the number of patients is dramatically increasing. We aimed to better characterize ICI-associated myositis patients and identify factors associated with poor outcome. Data were collected from the World Health Organization pharmacovigilance database of individual safety case reports (Uppsala, Sweden) through November 2018. Eventually, 277 myositis patients were identified, mostly receiving monotherapy in 83.4%. They harboured a specific phenotype with cardiotoxicity (20.9%, n=58) including myocarditis (n=38) and myasthenia gravis-like symptoms (n=44). The overall mortality was 21% (n=54/257). The mortality rate was significantly higher in patients with concurrent cardiotoxicity (53.7% vs 12.3%, p<0.0001) and in patients treated with combotherapy (anti-PD1 and anti-CTLA-4) compared to monotherapy (25.9% vs 19.6%, p=0.04). In multivariate analysis, cardiotoxicity and cancer progression were the two independent factors associated with fatal outcome (respectively, OR=9.7 p<0.0001 and OR=15.2 p= 0.0002). In the group of patients with fatal outcome, the median time of myositis onset was significantly shorter 18 days [14.5-23.5] vs 34 days [21-65] p=0.002 (data available in 88 patients). Mortality in patients with ICI-associated myositis is related to cardiotoxicity and cancer progression. Severe form occurs early after the first infusion of ICI.
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