Profiling Immune-Related Adverse Events Associated with Imatinib: A Two-Decade Real-World Safety Study Based on FDA Adverse Event Reporting System.

BACKGROUND

Emerging evidence suggests that imatinib may influence immune pathways and be associated with adverse events (AE) with potential immune involvement, some leading to treatment interruption or irreversible damage. However, systematic characterization remains limited.

METHODS

We analyzed FDA Adverse Event Reporting System data (2004-2024), extracting reports with imatinib as the primary suspect. Immune-related AEs were identified using standardized MedDRA queries. Disproportionality analyses were performed using reporting odds ratio (ROR), proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network. Signals meeting all thresholds were considered positive. ROR was the primary reference for signal strength.

RESULTS

A total of 15,748 patients experienced 31,400 target events, yielding 74 safety signals. Signals of organ dysfunction-particularly in the liver, kidney, and lung-were identified. High-signal with notable immune or inflammatory features included necrotizing panniculitis (ROR 164.69, 95% CI 90.65-299.22), inclusion body myositis, polyserositis, and chronic cutaneous lupus erythematosus. Frequent events like fluid retention and cytopenia were relatively nonspecific. Signals showed heterogeneity across sex and age subgroups and tended to occur in the mid-to-late treatment period.

CONCLUSIONS

Imatinib is associated with diverse signals with potential immune involvement, exhibiting age- and sex-related heterogeneity. Further prospective and mechanistic studies are warranted.