Toward the future management of patients with CML and Ph + ALL: real-world safety insights from dasatinib pharmacovigilance

Background Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, has transformed treatment for chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia. However, its broad kinase inhibition leads to distinct adverse events (AEs), requiring systematic post-marketing surveillance. Objective To evaluate dasatinib-associated AEs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and identify potential safety signals. Methods We extracted FAERS reports (Q1 2004–Q4 2024) listing dasatinib as the primary suspect drug, submitted by physicians or pharmacists. After data cleaning, AEs were coded using MedDRA terminology. Signal detection was performed with four disproportionality methods (ROR, PRR, BCPNN, MGPS). Time-to-onset was analyzed using Weibull models, with subgroup analyses by demographic and clinical characteristics. Results Among 7,213 cases, respiratory disorders were the most prominent signal (ROR = 2.74). A total of 1,951 significant signals were identified, 113 confirmed by all algorithms. Strongest disproportionality signals included blast cell proliferation (ROR = 518.94), primary effusion lymphoma (ROR = 181.38), and allogeneic bone marrow transplantation therapy (ROR = 171.48). Common AEs were pleural effusion ( n = 828, ROR = 35.87), hepatotoxicity ( n = 262, ROR = 29.17), and fluid retention ( n = 129, ROR = 14.49). Weibull analysis showed an early failure pattern (β = 0.64), with 25.6% of AEs within 30 days and 28.2% after 360 days. Subgroup analysis revealed pleural effusion across all demographics, while hematologic signals predominated in adults and elderly patients. Conclusion This large FAERS analysis characterized known respiratory complications of dasatinib, particularly pleural effusion, and identified several rare but potentially relevant safety signals hepatotoxicity, cardiovascular events, and novel AEs such as alveolar proteinosis and cytomegalovirus-related complications. The early failure pattern underscores the need for intensive monitoring during initiation and continued vigilance during long-term therapy. These findings provide real-world, hypothesis-generating evidence to optimize safety management and inform future clinical investigations, and should be interpreted with caution in view of the inherent limitations of spontaneous reporting data.