PMID- 34200673 OWN - NLM STAT- MEDLINE DCOM- 20210726 LR - 20231107 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 12 DP - 2021 Jun 10 TI - Myositis/Myasthenia after Pembrolizumab in a Bladder Cancer Patient with an Autoimmunity-Associated HLA: Immune-Biological Evaluation and Case Report. LID - 10.3390/ijms22126246 [doi] LID - 6246 AB - 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. FAU - Botta, Cirino AU - Botta C AUID- ORCID: 0000-0002-1522-4504 AD - Unit of Hematology, Azienda Ospedaliera "Annunziata", 87100 Cosenza, Italy. AD - Hematology Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90128 Palermo, Italy. FAU - Agostino, Rita Maria AU - Agostino RM AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Dattola, Vincenzo AU - Dattola V AD - Unit of Neurology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Cianci, Vittoria AU - Cianci V AD - Unit of Neurology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Calandruccio, Natale Daniele AU - Calandruccio ND AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Bianco, Giovanna AU - Bianco G AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Mafodda, Antonino AU - Mafodda A AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Maisano, Roberto AU - Maisano R AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Iuliano, Eleonora AU - Iuliano E AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Orizzonte, Giovanna AU - Orizzonte G AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Mazzacuva, Domenico AU - Mazzacuva D AD - Laboratory of Autoimmunity, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Falzea, Antonia Consuelo AU - Falzea AC AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Saladino, Rita Emilena AU - Saladino RE AD - HLA Tissue Typing Laboratory, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Giannicola, Rocco AU - Giannicola R AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Restifo, Giorgio AU - Restifo G AD - Nuclear Medicine Unit, Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Aguglia, Umberto AU - Aguglia U AUID- ORCID: 0000-0002-4574-2951 AD - Unit of Neurology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. FAU - Caraglia, Michele AU - Caraglia M AUID- ORCID: 0000-0003-2408-6091 AD - Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy. AD - Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, 83031 Ariano Irpino, Italy. FAU - Correale, Pierpaolo AU - Correale P AUID- ORCID: 0000-0003-2154-6734 AD - Unit of Oncology, Unit. Grand Metropolitan Hospital "Bianchi Melacrino Morelli", 89124 Reggio Calabria, Italy. LA - eng PT - Case Reports DEP - 20210610 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (HLA Antigens) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Aged MH - Antibodies, Monoclonal, Humanized/*adverse effects MH - Antineoplastic Agents, Immunological/*adverse effects MH - *Autoimmunity MH - HLA Antigens/*immunology MH - Humans MH - Male MH - Myasthenia Gravis/chemically induced/immunology/*pathology MH - Myositis/chemically induced/immunology/*pathology MH - Prognosis MH - Urinary Bladder Neoplasms/*drug therapy PMC - PMC8230397 OTO - NOTNLM OT - PD1-checkpoint inhibitors OT - class-I/II HLA OT - myasthenia OT - urothelial cancer COIS- The authors declare no conflict of interest. EDAT- 2021/07/03 06:00 MHDA- 2021/07/27 06:00 PMCR- 2021/06/10 CRDT- 2021/07/02 01:08 PHST- 2021/05/21 00:00 [received] PHST- 2021/06/03 00:00 [revised] PHST- 2021/06/07 00:00 [accepted] PHST- 2021/07/02 01:08 [entrez] PHST- 2021/07/03 06:00 [pubmed] PHST- 2021/07/27 06:00 [medline] PHST- 2021/06/10 00:00 [pmc-release] AID - ijms22126246 [pii] AID - ijms-22-06246 [pii] AID - 10.3390/ijms22126246 [doi] PST - epublish SO - Int J Mol Sci. 2021 Jun 10;22(12):6246. doi: 10.3390/ijms22126246.