Renal Safety Profile of BCR-ABL Tyrosine Kinase Inhibitors in a Real-Life Setting: A Study Based on Vigibase^®, the WHO Pharmacovigilance Database

Area of Science:

• Nephrology
• Pharmacology
• Oncology

Background:

• Tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) can affect kidney function due to off-target effects on renal tyrosine kinases.
• Real-world renal safety of CML TKIs requires evaluation using large safety databases.

Purpose of the Study:

• To assess the renal adverse drug reaction (ADR) profile of commonly used TKIs in CML.
• To identify potential renal safety signals associated with imatinib, dasatinib, nilotinib, bosutinib, and ponatinib.

Main Methods:

• A case/non-case study utilizing VigiBase®, the WHO global safety database.
• Analysis of suspected renal ADRs associated with five TKIs from November 2001 to June 2021.
• Disproportionality analysis using the reporting odds ratio to detect safety signals.

Main Results:

• 1409 cases of renal ADRs were identified, with imatinib accounting for half.
• Signals of disproportionate reporting for renal failure and fluid retention were observed for all five TKIs.
• Specific signals included nephrotic syndrome (dasatinib, nilotinib), renal artery stenosis (nilotinib, ponatinib), and thrombotic microangiopathy (dasatinib).

Conclusions:

• The study identified nephrotic syndrome as a novel safety signal for nilotinib.
• Post-marketing safety surveillance is crucial for detecting and managing TKI-associated renal adverse events.