(B-246) Safety of Immune Checkpoint Inhibitors: A Systematic Review of Disproportionality Analysis Studies

Background: Immunotherapy has fundamentally changed the treatment landscape for both solid and hematologic malignancies over the past decade. However, an evolving body of literature has reported immune-related adverse events (irAEs) involving several organs in patients treated with Immune checkpoint inhibitors (ICIs).

Objectives: The aim of our study was to systematically review published disproportionality analyses on ICIs, in order to summarize the current state of methodology and potential strengths of this analysis while highlighting safety signal generated for these pharmacological group.

Methods: A PubMed search was conducted on November 7, 2024, identified disproportionality analyses using a search algorithm combining terms related to ICIs and disproportionality analysis. Studies were included if they: 1) Employed disproportionality analysis in a pharmacovigilance database; 2) investigated any Immune Checkpoint Inhibitor (ICI); 3) focused on an ICI-adverse event pair; and 4) excluded studies solely focusing on drug-induced events without a specific ICI-adverse event pair. Data on results were categorized by adverse event type and further analyzed based on exposure and comparator. Databases such as Vigibase, Eudravigilance and the FAERS used in this study.

Results: A comprehensive PubMed search performed on November 7, 2024, identified 1899 published disproportionality analyses of ICIs. Of these, 57 analyses were eligible for inclusion in the study. The toxicity profiles of ICIs differ from the side effects of cytotoxic agents. Hypophysitis/Hypopituitarism is uniquely associated with the Anti-PD-L1/Anti-CTLA-4 combination. Endocrine disorders and immune-related complications are frequent across all ICI combinations. Guillain-Barré syndrome and myasthenia gravis have been reported, primarily with Nivolumab and Pembrolizumab. colitis, hepatitis, and arthritis. Immune-Related Skin Disorders such as rash, vitiligo, and dermatitis are frequently observed, particularly with Nivolumab and Pembrolizumab. Endocrinopathies conditions such as diabetes mellitus, adrenal insufficiency, and Hypophysitis are frequently observed with Nivolumab and Pembrolizumab.

Conclusions: Typically, these toxicities occur in all organs. The main organs affected are the skin, digestive, hepatic, lungs, rheumatologic, and endocrine. Most of the immune toxicity that occurs is low grade but some more severe toxicities can occur that require a rapid diagnosis and appropriate treatment. Disproportionality analysis in pharmacovigilance lacks standardized methods and interpretation, hindering reliable signal detection and requiring the development of clear guidelines, rigorous methodology, and collaborative efforts to improve patient safety.