Heterogeneity of thromboembolic risk across ALK inhibitors: a retrospective real-world study identifying crizotinib-specific signals and high-risk subpopulations.

Background: Patients with anaplastic lymphoma kinase (ALK)-positive malignancies increasingly rely on ALK inhibitors (ALKis) as first-line therapy, yet thromboembolism (TE) across the ALKi family and its impact on patients' safety remain incompletely characterized, particularly in the real-world populations. Objective: The aim of this study was to evaluate the real-world TE risks associated with ALKis using pharmacovigilance data mining and to identify and characterize the high-risk contributors to TE. Methods: We extracted 52,808 adverse event (AE) reports from the FDA Adverse Event Reporting System (2013-2024), including 17,124 ALKi-treated patients. TE signal strength was calculated via disproportionality analysis and presented by the lower limit of reporting odds ratio (ROR Results: Among ALKi users, 251 TE cases were identified. Crizotinib exhibited significant TE safety signals for embolism (ROR Conclusion: This study validates the elevated TE safety signal strength of crizotinib in the real-world settings, while no disproportionate TE signals were detected for other ALKi in the FAERS database. Clinicians could prioritize agent-specific risks, especially in older male patients and during early treatment phases.