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Renal Toxicity in Patients With CML After Discontinuation of TKIs

By: Sarah Campen, PharmD
Posted: Monday, July 13, 2020

Renal toxicity induced by tyrosine kinase inhibitor (TKI) use in patients with chronic myeloid leukemia (CML) may be associated with long-term TKI treatment, according to Shinya Kimura, MD, PhD, of Saga University, Japan, and colleagues. Their retrospective study, published in the International Journal of Hematology, revealed the toxicity may be irreversible, even after treatment discontinuation. The researchers also found that patients who received first-line treatment with imatinib had lower estimated glomerular filtration rates than patients treated with dasatinib or nilotinib, possibly due to the longer treatment duration associated with imatinib.

The analysis included data on 33 patients with CML in chronic phase. Participants were treated in the first-line setting with imatinib (n = 17), dasatinib (n = 11), and nilotinib (n = 5); the last TKIs used prior to discontinuation were imatinib (n = 5), dasatinib (n = 22), and nilotinib (n = 6).

A correlation between the estimated glomerular filtration rate at the time the TKI was discontinued and the duration of treatment with the TKI (P = .005) was observed, indicating that “long-term TKI treatment appears to induce renal toxicity.” The average estimated glomerular filtration rate decline until TKI discontinuation was 1.76 mL/min/1.73 m2 per year.

Patients who received imatinib as first-line treatment exhibited lower estimated glomerular filtration rates than those treated with dasatinib or nilotinib, which the study authors thought may be associated with the longer treatment duration associated with imatinib (P = .027). Renal function did not appear to improve after discontinuation of TKIs, as no significant increases in estimated glomerular filtration rate were seen in patients either with treatment-free remission or molecular relapse.

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