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Concurrent Imatinib Dosing With High-dose Methotrexate Leads to Acute Kidney Injury and Delayed Methotrexate

Lauren Pommert1, Nicole Liberio1, John S Ng2

  • 1Department of Pediatrics, Division of Hematology/Oncology/Blood and Marrow Transplantation, Medical College of Wisconsin and Children's Milwaukee, Milwaukee, WI.

Journal of Pediatric Hematology/Oncology
|May 14, 2020
PubMed

Insights

Imatinib use in pediatric leukemia patients may delay methotrexate clearance, causing kidney injury. Holding imatinib during high-dose methotrexate cycles reduces toxicity and hospital stays.

Area of Science:

  • Oncology
  • Pharmacology
  • Pediatrics

Background:

  • Imatinib (tyrosine kinase inhibitor) improves survival in pediatric Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL).
  • No formal drug interactions are listed between methotrexate and tyrosine kinase inhibitors.

Purpose of the Study:

  • To investigate the impact of imatinib on methotrexate clearance in pediatric patients with Ph+ B-ALL.
  • To evaluate the safety and efficacy of adjusting imatinib dosing during high-dose methotrexate (HDMTX) therapy.

Main Methods:

  • Retrospective analysis of four pediatric patients with Ph+ B-ALL receiving imatinib and HDMTX.
  • Monitoring methotrexate levels, renal function, and adverse events.
  • Comparison of outcomes during HDMTX cycles with and without concurrent imatinib.

Main Results:

  • Four patients experienced delayed methotrexate clearance and acute kidney injury during the first HDMTX cycle with imatinib.
  • Withholding imatinib during subsequent HDMTX cycles led to decreased acute kidney injury, faster methotrexate clearance, reduced toxicity, and shorter hospitalizations.
  • Escalated supportive care (hyperhydration, leucovorin) is recommended for patients on imatinib.

Conclusions:

  • Concurrent imatinib use can significantly delay methotrexate clearance in pediatric Ph+ B-ALL patients, increasing the risk of acute kidney injury.
  • Temporarily holding imatinib during HDMTX cycles is a viable strategy to mitigate toxicity and improve patient outcomes.
  • Close monitoring and adjusted supportive care are crucial for managing patients receiving both imatinib and HDMTX.

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