Real-World Creatinine-Based Estimates of Acute and Chronic Kidney Dysfunction in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Receiving Tyrosine Kinase Inhibitors.

Background: Anaplastic lymphoma kinase inhibitors (ALKi) are a mainstay of therapy for patients with advanced non-small cell lung cancers (NSCLC). ALKi are associated with increased serum creatinine, which may represent reduced renal tubular creatinine secretion and/or true acute kidney injury (AKI).

Methods: We performed a retrospective study of patients who received ALKi for NSCLC (2013-2022). The primary outcomes were incidence of AKI within 90 days of ALKi start and chronic kidney disease (CKD) within 1-year. AKI and CKD were defined via KDIGO criteria, using the CKD-EPI equation with creatinine (and cystatin C in a subcohort). We performed logistic regression for AKI risk factors and Kaplan-Meier analysis for overall survival (OS). Spline curves were generated for eGFR means over time.

Results: Among 114 NSCLC patients, median age 61 years; 53% were female; 191 ALKi treatments were initiated: Alectinib (n = 91), Crizotinib (n = 33), Ceritinib (n = 27), Brigatinib (n = 21) and Lorlatinib (n = 19). There were 20 (10%) AKI events within 90 days after ALKi initiation, with 4 treatment changes attributed to AKI. Twenty-eight (14%) patients developed CKD, with 10 treatment changes; none requiring dialysis. In multivariate analysis, hypertension and male sex were associated with AKI. OS did not differ by AKI status.

Conclusion: AKI/CKD events were frequent post-ALKi initiation (using creatinine-based eGFR), with a minority resulting in treatment change. Mean eGFR declined in the 90-days post-ALKi start. Most patients had mild CKD, with eGFR recovering postdrug cessation. AKI did not impact OS. Our findings suggest that most patients may continue ALKi therapy despite creatinine-based eGFR changes.