Myositis/myasthenia after pembrolizumab in a bladder cancer patient with an autoimmunity-associated HLA: Immune\u2013biological evaluation and case report

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\u2013biological 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

Could PD-1/PDL1 immune checkpoints be linked to HLA signature?

The outstanding clinical expansion of monoclonal antibodies (mAbs) to programmed cell death receptor-1 (PD-1) (nivolumab and pembrolizumab) and PD-1 ligand-1 (PDL-1) (atezolizumab, avelumab and durvalumab) has received an increasing level of interest regarding immunotherapy and multidrug combinations, for the treatment of a number of common human malignancies. Some patients treated with these agents receive remarkable benefits in term of quality of life, progression-free (PFS) and overall survival (OS). However, a significant percentage of these patients experience immune-related adverse events (irAEs), while others present with an ultra-rapid disease progression, defined as hyperprogression. Research in to the mechanisms related to these events is an active field of investigation worldwide, whose results are expected to provide new insights to design new combinations, to identify potentially responsive patients and to prevent irAEs\u2019 occurrenc