Renal dysfunction in patients with CML on long-term first-line TKI therapy: a single-center analysis

With life expectancies of patients with chronic myeloid leukemia (CML) now approaching those of the general population under tyrosine kinase inhibitor (TKI) therapy, understanding long-term treatment-related toxicities becomes paramount. Although imatinib's nephrotoxic potential is established, the renal safety profiles of second-generation TKIs-dasatinib, nilotinib, and flumatinib-remain incompletely characterized.

This single-center retrospective study analyzed renal function trajectories in 348 patients with CML receiving first-line imatinib, dasatinib, nilotinib, or flumatinib. Renal function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Mixed-effects models incorporating treatment group, time, and their interaction as fixed effects were used to formally compare eGFR trajectories across treatment groups. Chronic renal adverse events and acute kidney injury were also evaluated.

Formal comparison of eGFR trajectories across treatment groups revealed a significant time × treatment interaction, indicating differential renal function changes among the 4 TKIs. Significant serum creatinine elevation and eGFR decline were observed in imatinib and flumatinib groups, contrasting with stable creatinine and divergent eGFR patterns in dasatinib (slight increase) and nilotinib (decline) groups. The incidence of chronic renal adverse events varied substantially across cohorts-12.3% (imatinib), 2.6% (nilotinib), 4.3% (dasatinib), and 9.6% (flumatinib). Notably, among 3 documented acute kidney injury cases, all occurred during flumatinib treatment. Furthermore, treatment-free remission achievement did not confer significant renal function recovery, suggesting potential irreversibility of established renal damage.

TKIs exhibit differential renal safety profiles, underscoring the critical importance of individualized TKI selection based on baseline renal status and implementation of rigorous renal monitoring protocols throughout treatment duration.