Beyond haematological control: Long-term renal outcomes of imatinib therapy in chronic myeloid leukaemia.

Abstract

6581 Background: Imatinib has transformed outcomes in chronic myeloid leukaemia (CML), enabling long-term survival and durable molecular responses. With therapy often extending over decades, late toxicities affecting organ function have gained increasing importance. However, real-world data on long-term renal outcomes with prolonged imatinib exposure remain limited. Objectives: To evaluate long-term changes in renal function in patients with CML receiving imatinib therapy for at least 10 years. Methods: This retrospective observational study included patients with CML treated with imatinib for ≥10 years at a single tertiary care centre. Clinical and treatment-related data were obtained from medical records. Renal function at baseline and at latest follow-up was assessed using estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI formula. Data on diabetes and hypertension were collected. Patients with pre-existing chronic kidney disease, those receiving chemotherapy, those diagnosed with a second malignancy and patients in treatment-free remission (TFR) were excluded. Results: A total of 440 patients were analysed. The median age at diagnosis was 36 years (range, 5–70), with a male-to-female ratio of 1.39:1. At diagnosis, 95% were in chronic phase. Sokal risk stratification classified 32%, 31%, and 37% of patients as low, intermediate, and high risk, respectively. The median duration of imatinib therapy was 15 years (range, 10–24), with a median daily dose of 400 mg (range, 200–800 mg). At last follow-up, 91% of patients had achieved major molecular response. Overall, 62 patients (14%) developed a clinically significant decline in renal function (eGFR <60 mL/min/1.73 m²). In this subgroup, median eGFR declined from 90 range, 70-122) to 44 mL/min/1.73 m² (range, 13-54); representing a median reduction of 46 mL/min over 15 years (approximately 3 mL/min/year). Comorbidities were present in 11 patients (18%). A greater decline in eGFR was observed among males (p<0.001), patients aged <35 years at diagnosis (p<0.0001), and those achieving major molecular response (p<0.0002). Treatment modification was undertaken in<37 patients (60%), including TFR in 13 (21%), dose reduction in 20 (32%), and switching to an alternate tyrosine kinase inhibitor in 4 (6%). Partial renal recovery was documented in 9 patients (24%). All patients in whom TFR was attempted continue to maintain TFR at last follow-up. Conclusions: Long-term imatinib therapy is associated with a gradual but clinically meaningful decline in renal function in a subset of patients with CML. Dose modification, switching TKIs, or attempting TFR may result in partial reversibility, without compromising disease control. These findings highlight the importance of long-term renal monitoring and treatment optimisation in patients with sustained molecular responses.