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TKIs appear safe for patients with CML
Acute kidney injury occurred in a small proportion of patients with chronic-phase chronic myeloid leukemia treated with tyrosine kinase inhibitors, according to study results published in Cancer.
Tyrosine kinase inhibitors (TKIs) such as imatinib (Gleevec, Novartis), dasatinib (Sprycel, Bristol-Myers Squibb) and nilotinib (Tasigna, Novartis) have improved outcomes with fewer adverse events for patients with CML, However, TKIs also have off-target effects, and some studies have indicated a possible association with acute kidney injury and chronic kidney disease.
Jorge E. Cortes, MD, deputy chair of the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues sought to evaluate the incidence of acute kidney injury and chronic kidney disease in patients with CML treated with TKIs as initial therapy. The researchers evaluated the glomerular filtration rate (GFR) changes over time and their impact on outcomes.
Jorge E. Cortes
The analysis included 468 patients with CML who were treated with imatinib, dasatinib or nilotinib between 2001 and 2011 at MD Anderson Cancer Center.
Nineteen patients (4%) had a TKI-associated acute kidney injury during follow-up. Among those patients, 84% were treated with imatinib, compared with 16% who were treated with a different TKI (P = .014).
Overall, 58 patients (14%) developed new-onset chronic kidney disease while they were receiving a TKI, the majority of whom received imatinib (84% vs. 16%; P < .001).
Other than treatment with imatinib, age, history of hypertension and diabetes also appeared associated with the development of chronic kidney disease (P < .01 for all). However, imatinib most significantly increased the risk for chronic kidney disease of the four factors (OR = 8.3; 95% CI, 3.5-19.4).
Researchers noted acute kidney injury and chronic kidney disease did not have a significant impact on response rates or survival.
Patients without chronic kidney disease at baseline experienced a reduction in GFR over time if they received imatinib, but imatinib did not cause a significant reduction in the GFR of patients with a history of chronic kidney disease.
All of the TKIs evaluated in the study increased the mean GFR after 3 months of treatment, with nilotinib demonstrating the most significant increase (P < .001). At the end of 24 months, the mean GFR difference from baseline was lower for imatinib (1 mL/min/1.73 m2) and higher in the dasatinib cohort (4 mL/min/1.73 m2). The mean GFR increase from baseline to 24 months was 10 mL/min/1.73 m2 among patients treated with nilotinib.
“Acute kidney injury occurs in a small percentage of patients treated with TKIs and particularly in those treated with imatinib,” Cortes and colleagues wrote. “The effects tend to be mild and usually requires no treatment interruptions or changes to the TKI.
“Still, it is important to monitor renal function, particularly early during the course of therapy, because most acute kidney injury cases occur during the first 3 months of therapy.” – by Anthony SanFilippo
Disclosure: The researchers report research funding from and consulting/advisory roles with Ariad, Bristol-Myers Squibb, Novartis, Pfizer and Teva.