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ORIGINAL RESEARCH article

Front. Pharmacol.

Sec. Pharmacology of Anti-Cancer Drugs

Volume 16 - 2025 | doi: 10.3389/fphar.2025.1676800

This article is part of the Research TopicDiagnostic, Prognostic and Predictive Markers in LeukemiaView all 5 articles

Correlation Analysis Between Plasma Concentration of Nilotinib and Clinical Efficacy and Safety in Patients with Chronic Myeloid Leukemia : a single–center retrospective cohort study

Provisionally accepted
Ying  LiuYing Liu1Taoyan  LinTaoyan Lin2Boxin  ZhaoBoxin Zhao2Yilei  LiYilei Li2*Ping  ZhengPing Zheng2*
  • 1Nanfang Hospital, Southern Medical University, Guangzhou, China
  • 2Southern Medical University Nanfang Hospital, Guangzhou, China

The final, formatted version of the article will be published soon.

Objective: This study aimed to investigate the correlation between nilotinib plasma concentrations and clinical efficacy and safety in patients with chronic myeloid leukemia (CML), thereby supporting personalized therapeutic optimization. Methods: We conducted a retrospective cohort study of 121 CML patients receiving nilotinib with therapeutic drug monitoring (TDM) at Nanfang Hospital of Southern Medical University between March 2021 and February 2024. Major molecular response (MMR) and adverse events (CTCAE v5.0) were analyzed against concentrations. Receiver operating characteristic (ROC) curves defined thresholds; dose-normalized exposure (Cnorm=Cmin/(Dose/600mg)) addressed TDM bias. Results: The effective group showed higher nilotinib concentrations than those in the ineffective group (1036.40±463.67 vs 737.14±518.97 ng·mL-1; P<0.001), confirmed post-normalization (1045.10±468.08 vs 858.34±723.66 ng·mL-1; P<0.05). The ROC-derived efficacy threshold was 636.99 ng·mL-1 (AUC=0.693, 95% CI: 0.596–0.791), which was identical after normalization (AUC=0.655, 95% CI: 0.554–0.755). Although adverse events were common (76.9% of patients), they showed no overall concentration dependence (P = 0.288). However, hyperbilirubinemia risk was significantly elevated in patients with concentrations > 1273.98 ng·mL-1 cohort (50.0% vs 20.0-22.6%; P=0.030), with a toxicity threshold identified at 1290.34 ng·mL-1 (AUC=0.656, 95% CI: 0.540-0.771). Longer treatment duration was also associated with higher drug exposure (P=0.029).Conclusion: Nilotinib concentrations predict MMR attainment independent of TDM-driven dose adjustments (validated via Cnorm). We recommend targeting early-phase concentrations >636.99 ng·mL-1, monitoring bilirubin above 1290.34 ng·mL-1, and integrating dynamic TDM with pharmacogenetic profiling.

Keywords: Nilotinib1, Chronic myeloidleukemia2, Plasma Concentration3, TDM4, Efficacy5, Safety6

Received: 31 Jul 2025; Accepted: 28 Aug 2025.

Copyright: © 2025 Liu, Lin, Zhao, Li and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yilei Li, Southern Medical University Nanfang Hospital, Guangzhou, China
Ping Zheng, Southern Medical University Nanfang Hospital, Guangzhou, China

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