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

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.

Figure 1

(A) CT/PET scan performed prior to and after three treatment cycles of pembrolizumab showed a good disease control with volume reduction in all the involved sites. (B) CT/PET scan performed during the follow-up (after 8 months from the last pembrolizumab administration) demonstrated a further reduction in cancer metabolism coupled with a sclerotic reaction. Arrows indicate the point where SUV reduction is more evident. (C) Cartoon representing the possible mechanism responsible for (muscle) immune-related adverse events (irAEs). Pembro: pembrolizumab; AA: auto-antigens; TAA: tumor-associated antigens.