Do peripheral neuropathies differ among immune checkpoint inhibitors? Reports from the European post-marketing surveillance database in the past 10 years

• Published in: Frontiers in immunology Vol. 14; p. 1134436
• Main Authors: Ruggiero, Rosanna, Balzano, Nunzia, Di Napoli, Raffaella, Fraenza, Federica, Pentella, Ciro, Riccardi, Consiglia, Donniacuo, Maria, Tesorone, Marina, Danesi, Romano, Del Re, Marzia, Rossi, Francesco, Capuano, Annalisa
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.03.2023
• Subjects: Antineoplastic Agents, Immunological - therapeutic use; Drug-Related Side Effects and Adverse Reactions - drug therapy; Drug-Related Side Effects and Adverse Reactions - epidemiology; Guillain-Barre Syndrome - chemically induced; Guillain-Barre Syndrome - epidemiology; Humans; immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune System Diseases - drug therapy; immune-related adverse events; Immunology; immunotherapy; Neoplasms; neurological toxicity; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - epidemiology; Pharmacovigilance; post-marketing surveillance; Quality of Life; translational research; post-marketing surveillance; immune-related adverse events; immunotherapy; translational research; immune checkpoint inhibitors; neurological toxicity; peripheral neuropathies
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1134436

Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs.