Characterizing bleeding adverse events associated with BCR-ABL tyrosine kinase inhibitors: insights from FAERS...

Bleeding is a potentially serious but underrecognized adverse event associated with BCR-ABL tyrosine kinase inhibitors (TKIs). Although hematologic and cardiovascular toxicities of these agents have been extensively investigated, the spectrum and characteristics of bleeding-related adverse events in real-world settings remain incompletely understood. This study aimed to characterize bleeding-related adverse event signals associated with five BCR-ABL TKIs using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

A pharmacovigilance study was conducted using FAERS data from 2004Q1 to 2026Q1. Reports involving imatinib, dasatinib, nilotinib, ponatinib, and bosutinib as primary suspected drugs were identified. Bleeding-related adverse events were screened using Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs). Disproportionality analysis was performed using the reporting odds ratio (ROR) method to detect potential bleeding signals. Demographic characteristics, clinical outcomes, and distributions of bleeding-related signals across System Organ Classes (SOCs) were further evaluated.

Among 20, 326, 782 deduplicated FAERS reports, 124, 797 reports involving BCR-ABL TKIs were identified, including 3, 648 bleeding cases and 121, 149 non-bleeding cases. Bleeding reports were associated with higher proportions of hospitalization (19.8% vs. 14.4%) and life-threatening outcomes (2.7% vs. 1.5%) than non-bleeding reports. A total of 64 positive bleeding-related signals were detected across the five study drugs. Gastrointestinal disorders, nervous system disorders, and eye disorders represented the most frequently involved organ systems. Gastrointestinal haemorrhage, cerebral haemorrhage, and eye haemorrhage were recurrent signals detected across multiple TKIs. Several gastrointestinal bleeding-related signals were identified for dasatinib, including enterocolitis haemorrhagic (ROR = 28.98), while multiple bleeding-related PTs involving diverse organ systems were detected for imatinib. In addition, several uncommon PTs demonstrated elevated disproportionality estimates, although these findings were based on relatively small numbers of reports.

Bleeding-related adverse events associated with BCR-ABL TKIs involve multiple organ systems and encompass a broad spectrum of clinical manifestations. Gastrointestinal, neurological, and ocular haemorrhagic events accounted for the majority of detected signals. These findings provide real-world evidence regarding the characteristics of bleeding-related adverse events associated with BCR-ABL TKIs and may contribute to pharmacovigilance monitoring, individualized safety management, and future investigations of haemorrhagic toxicity during TKI therapy.