Myositis/Myasthenia after Pembrolizumab in a Bladder Cancer Patient with an Autoimmunity-Associated HLA: Immune-Biological Evaluation and Case Report

Int J Mol Sci. 2021 Jun 10;22(12):6246. doi: 10.3390/ijms22126246.

Abstract

Pembrolizumab (mAb to PD-1) has been recently approved for the therapy of pretreated urothelial cancer. Despite the efficacy, it is often accompanied by unpredictable and sometime severe immune-related (ir) adverse events (AEs). Here, we report the clinical and immune-biological characterization of a patient with a metastatic bladder cancer who developed myositis signs (M) and a myasthenia-like syndrome (MLS) during treatment with pembrolizumab. The patient presented an autoimmunity-associated HLA haplotype (HLA-A*02/HLA-B*08/HLA-C*07/HLA-DRB1*03) and experienced an increase in activated CD8 T-cells along the treatment. The symptomatology regressed after pembrolizumab discontinuation and a pyridostigmine and steroids-based therapy. This is the first report of concurrent M and MLS appearance in cancer patients receiving pembrolizumab. More efforts are needed to define early the risk and the clinical meaning of irAEs in this setting.

Keywords: PD1-checkpoint inhibitors; class-I/II HLA; myasthenia; urothelial cancer.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents, Immunological / adverse effects*
  • Autoimmunity*
  • HLA Antigens / immunology*
  • Humans
  • Male
  • Myasthenia Gravis / chemically induced
  • Myasthenia Gravis / immunology
  • Myasthenia Gravis / pathology*
  • Myositis / chemically induced
  • Myositis / immunology
  • Myositis / pathology*
  • Prognosis
  • Urinary Bladder Neoplasms / drug therapy*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • HLA Antigens
  • pembrolizumab