Disproportionality analysis of ALK inhibitor-induced hemolytic adverse events: a pharmacovigilance study using the FDA Adverse Event Reporting System Database

Anaplastic lymphoma kinase (ALK) inhibitors have transformed treatment for ALK-rearranged malignancies, particularly non-small cell lung cancer, by disrupting oncogenic signalling. However, hematologic adverse effects, including hemolysis, have emerged as concerns, especially with alectinib. This study evaluates the prevalence of hemolytic events associated with ALK inhibitors using FDA Adverse Event Reporting System (FAERS) data. A retrospective pharmacovigilance analysis was conducted using FAERS data (2013-2023). Disproportionality analysis with OpenVigil 2.1 assessed associations between ALK inhibitors and hemolysis-related events. Reporting odds ratios (RORs) were calculated, with statistical significance defined as ROR > 2.00 and a lower 95% confidence interval (CI) bound > 1.00. Alectinib exhibited strong associations with hemolysis (ROR 24.01, 95% CI: 17.88-32.24; 45 reports) and bilirubin increase (ROR 18.86, 95% CI: 15.92-22.34; 138 reports). Crizotinib and ceritinib showed weaker signals, while brigatinib and lorlatinib had no significant associations. The findings highlight alectinibs potential hemolytic risk, necessitating hematologic monitoring. Proposed mechanisms include immune-mediated hemolysis, direct cytotoxicity, and metabolic variability. Routine hemoglobin and bilirubin assessments, along with clinical vigilance, are essential. Further studies are needed to elucidate mechanisms of causality and optimize patient safety.