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. 2015 Nov 1;121(21):3894-904.
doi: 10.1002/cncr.29587. Epub 2015 Jul 28.

Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Musa Yilmaz  1 , Amit Lahoti  2 , Susan O'Brien  3 , Graciela M Nogueras-González  4 , Jan Burger  3 , Alessandra Ferrajoli  3 , Gautam Borthakur  3 , Farhad Ravandi  3 , Sherry Pierce  3 , Elias Jabbour  3 , Hagop Kantarjian  3 , Jorge E Cortes  3
Affiliations

Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Musa Yilmaz et al. Cancer. .

Abstract

Background: Chronic use of tyrosine kinase inhibitors (TKIs) may lead to previously unrecognized adverse events. This study evaluated the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic-phase (CP) chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and nilotinib.

Methods: Four hundred sixty-eight newly diagnosed CP CML patients treated with TKIs were analyzed. The molecular and cytogenetic response data, creatinine, and glomerular filtration rate (GFR) were followed from the start of therapy to the last follow-up (median, 52 months). GFR was estimated with the Modification of Diet in Renal Disease equation.

Results: Nineteen patients (4%) had TKI-associated AKI. Imatinib was associated with a higher incidence of AKI in comparison with dasatinib and nilotinib (P = .014). Fifty-eight patients (14%) developed CKD while they were receiving a TKI; 49 of these patients (84%) did so while they were being treated with imatinib (P < .001). Besides imatinib, age, a history of hypertension, and diabetes mellitus were also associated with the development of CKD. In patients with no CKD at the baseline, imatinib was shown to reduce GFR over time. Interestingly, imatinib did not cause a significant decline in the GFRs of patients with a history of CKD. Imatinib, dasatinib, and nilotinib increased the mean GFR after 3 months of treatment, and nilotinib led with the most significant increase (P < .001). AKI or CKD had no significant impact on overall cytogenetic and molecular response rates or survival.

Conclusions: The administration of TKIs may be safe in the setting of CKD in CP CML patients, but close monitoring is still warranted.

Keywords: chronic myeloid leukemia (CML); dasatinib; glomerular filtration rate changes; imatinib; kidney injury; nilotinib; outcome; tyrosine kinase inhibitor.

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Figures

Figure 1
Figure 1. GFR Changes in CML Patients without CKD at Baseline
(A) Mean GFR Trend Over time (B) Mean GFR Difference from Baseline GFR, glomerular filtration fate; CML, chronic myeloid leukemia; CKD, chronic kidney disease; n, number of patients (at the start of treatment) . Data are mean [95% CI]. * p < 0.05 vs. baseline, * * p <0.01 vs. baseline, * * * p < 0.001 vs. baseline by paired t –test.
Figure 1
Figure 1. GFR Changes in CML Patients without CKD at Baseline
(A) Mean GFR Trend Over time (B) Mean GFR Difference from Baseline GFR, glomerular filtration fate; CML, chronic myeloid leukemia; CKD, chronic kidney disease; n, number of patients (at the start of treatment) . Data are mean [95% CI]. * p < 0.05 vs. baseline, * * p <0.01 vs. baseline, * * * p < 0.001 vs. baseline by paired t –test.
Figure 2
Figure 2. GFR Changes in CML Patients with CKD at Baseline
(A) Mean GFR Trend Over time (B) Mean GFR Difference from Baseline GFR,glomerular filtration rate; CML, chronic myeloid leukemia; CKD, chronic kidney disease; n, number of patients (at the start of treatment). Data are mean [95% CI]. * p < 0.05 vs. baseline by paired t –test.
Figure 2
Figure 2. GFR Changes in CML Patients with CKD at Baseline
(A) Mean GFR Trend Over time (B) Mean GFR Difference from Baseline GFR,glomerular filtration rate; CML, chronic myeloid leukemia; CKD, chronic kidney disease; n, number of patients (at the start of treatment). Data are mean [95% CI]. * p < 0.05 vs. baseline by paired t –test.
Figure 3
Figure 3
GFR Changes in CML Patients Treated with High or Standard Dose of Imatinib GFR, glomerular filtration rate; CML, chronic myeloid leukemia; n, number of patients (at the start of treatment) P value calculated by repeated-measures ANOVA
Figure 4
Figure 4
Overall (A), Event Free (B) and Transformation Free (C) Survival of CML patients with or without AKI determined by Kaplan-Meier survival method. CML, chronic myeloid leukemia; AKI, acute kidney injury
Figure 4
Figure 4
Overall (A), Event Free (B) and Transformation Free (C) Survival of CML patients with or without AKI determined by Kaplan-Meier survival method. CML, chronic myeloid leukemia; AKI, acute kidney injury
Figure 4
Figure 4
Overall (A), Event Free (B) and Transformation Free (C) Survival of CML patients with or without AKI determined by Kaplan-Meier survival method. CML, chronic myeloid leukemia; AKI, acute kidney injury
Figure 5
Figure 5
Overall (A), Event Free (B) and Transformation Free (C) Survival of CML patients with or without CKD determined by Kaplan-Meier survival method CML, chronic myeloid leukemia; CKD, chronic kidney
Figure 5
Figure 5
Overall (A), Event Free (B) and Transformation Free (C) Survival of CML patients with or without CKD determined by Kaplan-Meier survival method CML, chronic myeloid leukemia; CKD, chronic kidney
Figure 5
Figure 5
Overall (A), Event Free (B) and Transformation Free (C) Survival of CML patients with or without CKD determined by Kaplan-Meier survival method CML, chronic myeloid leukemia; CKD, chronic kidney
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