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Abstract: FR-PO279

Acute and Chronic Kidney Dysfunction Associated with Anaplastic Lymphoma Kinase (ALK) Inhibitors

Session Information

Category: Onconephrology

  • 1700 Onconephrology


  • Rao Ullur, Avinash, University of Toronto, Toronto, Ontario, Canada
  • Pinard, Louis, Universite de Montreal, Montreal, Quebec, Canada
  • Everest, Louis C., University Health Network, Toronto, Ontario, Canada
  • Khan, Khaleeq, University Health Network, Toronto, Ontario, Canada
  • Zhan, Luna Jia, University Health Network, Toronto, Ontario, Canada
  • Liu, Geoffrey, University Health Network, Toronto, Ontario, Canada
  • Kitchlu, Abhijat, University of Toronto, Toronto, Ontario, Canada

Anaplastic Lymphoma Kinase (ALK) inhibitors have marked activity against ALK-positive non-small cell lung cancers (NSCLC). Kidney adverse effects of ALK inhibitors have been increasingly reported, though some may relate to impairment of creatinine secretion.


We performed a retrospective observational study of patients who received ALK inhibitors for NSCLC between 2010-2022. The primary outcome was incidence of acute kidney injury (AKI) within 90 days of ALK start, and chronic kidney disease (CKD) during treatment. AKI and CKD were defined via KDIGO criteria, using the creatinine-based CKD-EPI equation. We performed logistic regression for AKI risk factors and used Kaplan-Meier analysis to assess overall survival (OS) by AKI status. Spline curves were generated to estimate eGFR means over time.


Among 149 Stage IIIB/IV NSCLC patients, median age was 60 years; 56% were female; 269 different TKIs were initiated: Alectinib (n=118), Ceritinib (n=30), Brigatinib (n=27), Crizotinib (n=68) and Lorlatinib (n=26). There were a total of 22 (15%) AKI events in the 90 days after initiating ALK inhibitors with 5 patients requiring treatment change due to kidney function. Figure 1 shows eGFR changes after ALK inhibitor initiation and termination. A total of 25(17%) patients developed CKD, 9 leading to treatment change. The mean eGFR for patients on Alectinib and Ceritinib was generally lower than Crizotinib. Age, hypertension, and diabetes were associated with AKI [adjusted OR (95%CI): 1.04 (1.00,1.08), 3.74 (1.50,9.54), 4.20 (1.55,11.2)]. OS did not differ by AKI status (Figure 1c).


There was a substantial number of AKI/CKD events observed, with a minority resulting in treatment change. Mean creatinine-based eGFR declined in the first 3 months post-ALK inhibitor start, but most patients had mild CKD during treatment, with eGFR recovering post-drug cessation. AKI did not impact OS. Our findings suggest that most patients may continue ALK TKI therapy despite kidney function changes.