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

Abstract

Background: Alongside their BCR-ABL specificity, TKIs used in chronic myeloid leukemia also target other tyrosine kinases expressed in the kidney such as PDGFR, c-KIT, SRC, and VEGFR, which may result in specific renal adverse drug reaction (ADR). To evaluate the renal safety profile in real-life conditions, a case/non-case study was performed on VigiBase®, the WHO global safety database. Methods: From 7 November 2001 to 2 June 2021, all cases in which the involvement of imatinib, dasatinib, nilotinib, bosutinib, and ponatinib was suspected in the occurrence of renal ADR were extracted from VigiBase®. Disproportionality analyses were assessed using the reporting odds ratio. Results: A total of 1409 cases were included. Imatinib accounts for half of the reported cases. A signal of disproportionate reporting (SDR) of renal failure and fluid retention was found for the five TKIs. Only dasatinib and nilotinib were related to an SDR for nephrotic syndrome. Nilotinib and ponatinib were related to an SDR for renal artery stenosis, while dasatinib was related to an SDR for thrombotic microangiopathy. No SDR for tubulointerstitial nephritis was observed. Conclusion: This study identified a new safety signal, nephrotic syndrome, for nilotinib and highlights the importance of post-marketing safety surveillance.

Renal Disorders with Oral Tyrosine Kinase Inhibitors in Metastatic Colorectal Cancer: An Analysis from the FDA Adverse Event Reporting System Database

“…The findings of this analysis revealed a higher association between renal ADRs and males, with an equal distribution between the adult and elderly population, compared to other cases. Previous studies have indicated that men may have a higher risk of developing renal impairment with targeted therapies than women [ 25 , 26 ]. This observation could be attributed to testosterone, which has been implicated in the progression of chronic kidney disease (CKD) and the worsening of kidney function in men [ 27 ].…”

“…Renal ADRs were predominantly classified as serious compared to other reported ADRs, as evidenced by the literature data on TKIs, in which a significant proportion (79%) of renal reports were serious [ 26 ]. In contrast to the previous pharmacovigilance study, a clinical trial reported serious renal disorders of grade 3 in only 10% of patients [ 31 ].…”

“…The median TTO for renal ADRs was found to be higher with ENC than REG. In the literature, the median TTOs for all TKIs varied significantly, ranging from 26 days to 684 days for renal disorders [ 26 , 34 ]. This greater difference could be attributed to the fact that different TKIs, including ENC and REG, may have distinct renal effects and toxicity profiles, leading to variations in the occurrence of serious renal disorders.…”

Neurocognitive impairment in females with breast cancer treated with endocrine therapy and CDK4/6 inhibitors: a pharmacovigilance study using the World Health Organization’s database

“…Finally, abemaciclib and ribociclib are reported more recently, and the number of reports is lower. However, the design of disproportionality analyses enables to detect signals with a low number of AEs (Cellier et al, 2023). Moreover, there was no trend toward significance for abemaciclib and ribociclib that might suggest a lack of power.…”