Investigators reported that the tyrosine kinase inhibitor dasatinib, commonly used to treat chronic myeloid leukemia (CML), was associated with nephrotoxicity in 10% of 32 patients with CML being treated with dasatinib in a multicenter, retrospective clinical study conducted to determine the incidence of kidney injury in this population. Researchers believe this study may impact clinical practice, possibly changing the standard of care and introducing new safety warnings for dasatinib. These study findings were published by Adegbite et al in the Clinical Journal of the American Society of Nephrology.
The investigators examined glomerular injury through urine albumin-creatinine (UAC) ratio in 82 patients with CML who had been continuously taking a tyrosine kinase inhibitor for at least 90 days. Among these patients, 32 participants were treated with dasatinib and 50 were treated with other, similar drugs.
Significantly elevated levels of proteinuria were identified in patients receiving dasatinib, with 10% of participants exhibiting severe levels that were later seen to decrease upon cessation of dasatinib. No participant in the cohort that did not receive dasatinib showed severe proteinuria. Widespread kidney damage in patients given dasatinib was also confirmed by kidney biopsy. They compared mean differences in UAC ratio, in addition to studying proteinuria.
The researchers pointed out that the incidence of kidney injury is a previously unknown severe side effect of this drug. Patients taking dasatinib are currently not screened for nephrotoxicity or kidney dysfunction—potentially making them susceptible to chronic kidney disease.
According to the investigators, oncologists prescribing dasatinib may be advised to monitor patients for kidney function or proteinuria and engage a nephrologist to assist in their care, based on these findings. It is also likely that the presence of proteinuria in this setting may result in changes in therapy, especially if proteinuria is severe. Furthermore, the researchers believe these findings suggest current clinical care, screening guidelines, and U.S. Food and Drug Administration guidance on adverse events may need to be updated. The investigators noted that larger prospective clinical studies are needed to help identify which patients may be susceptible to this type of injury [proteinuria] and design alternative treatment strategies.
DISCLOSURE: This work was supported by the National Institutes of Diabetes and Digestive and Kidney Diseases (R01 DK118222). For full disclosures of the study investigators, visit journals.lww.com/cjasn.