Long-term imatinib therapy leads to significant reduction in GFR Free

Background

Chronic Myeloid Leukemia (CML) is primarily treated with Tyrosine Kinase Inhibitors (TKIs), with Imatinib (IM) being the first-line therapy for over two decades. While its efficacy and long-term survival benefits are well established, the long-term impact on renal function remains inadequately studied, especially in Indian patients. Previous reports suggest a progressive decline in estimated glomerular filtration rate (eGFR) in patients on prolonged IM therapy, raising concerns regarding chronic kidney disease (CKD) risk in this population. The KITE Study (Kidney Impact of Ten-Year Exposure) aims to evaluate the renal function of CML patients on IM for over 10 years.Methods

This multicentric retrospective analysis from 9 contributing hematology centers, all part of the Hematology Cancer Consortium (HCC), a non-government registry from India, evaluated baseline and current biochemical and demographic data and calculated eGFR at two time points in patients who had received IM as first-line TKI for CML-CP for a minimum of 10 continuous years. Other variables analyzed included molecular remission status and comorbidities (diabetes mellitus [DM], hypertension [HTN], and coronary artery disease [CAD]). Patients with pre-existing CKD, TKI switching, HSCT, or enrollment in TFR trials were excluded. eGFR was calculated at baseline and last follow-up using the CKD-EPI formula and expressed in ml/min.Results

Total of 223 patients aged ≥18 years were analyzed. Median age at diagnosis was 40 years (18-81), 148 (66.4%%) were males and median IM exposure was 13 years (range 10–25). At final follow-up, 89% of patients were in major molecular remission (MMR). The prevalence of comorbidities was: DM 5.8%, HTN 9.5%, and CAD 1.8%.

- Median eGFR declined from 103 ml/min (baseline) to 89.5 ml/min (follow-up)

- This represents a median reduction of 14 ml/min over 13 years, equivalent to ~1.08 ml/min/year.

- Female patients had a significantly lower median GFR decline compared to males (8 vs. 16 ml/min; p = 0.0213)

- No statistically significant difference in GFR decline was observed with respect to age group (≤30 vs. >30 years; p = 0.9766), MMR status (p = 0.8402), HTN (p = 0.6359), DM (p = 0.1644), or CAD (p = 0.5581).Discussion

While hematological, gastrointestinal, and dermatological toxicities of IM are well recognized and monitored due to their impact on tolerance and compliance, renal function deterioration with long-term IM exposure is often under-recognized. In contrast to the ~0.32 ml/min/year decline observed in age-matched general populations, this study reveals a 3-fold greater decline in eGFR with prolonged IM use. Importantly, male sex was associated with a significantly greater decline in GFR, highlighting the need for sex-specific renal monitoring strategies. To the best of our knowledge, this is the largest study to date evaluating renal function decline in long-term IM-exposed CML patients. These findings underscore the importance of routine renal monitoring and reconsideration of treatment goals such as TFR in long-term IM-treated patients. Further studies comparing other TKIs are warranted to guide TKI selection, especially in patients unable to achieve TFR.