| Title |
Central nervous system penetration of imatinib in acute lymphoblastic leukemia: Pharmacokinetic analysis and clinical implications |
| Authors |
Rasmussen, Anna Sofie Buhl ; Rank, Cecilie Utke ; Christensen, Ib Jarle ; Weimann, Allan ; Hansen, Kasper ; Thastrup, Maria ; Yang, Tianwu ; Lund, Trine Meldgaard ; Wik, Hilde Skuterud ; Vogt, Hartmut ; Norén-Nyström, Ulrika ; Vaitkevičienė, Goda Elizabeta ; Albertsen, Birgitte Klug ; Wehner, Peder Skov ; Als-Nielsen, Bodil ; Andersen, Christen Lykkegaard ; Dalhoff, Kim ; Schmiegelow, Kjeld |
| DOI |
10.1007/s00280-026-04914-9 |
| Full Text |
|
| Is Part of |
Cancer chemotherapy and pharmacology.. Springer. 2026, vol. 96, iss. 1, art. no. 65, p. [1-11].. ISSN 0344-5704. eISSN 1432-0843 |
| Keywords [eng] |
acute lymphoblastic leukemia ; central nervous system ; cerebrospinal fluid ; imatinib ; pediatric ; young adults |
| Abstract [eng] |
Purpose: Tyrosine kinase inhibitors (TKIs) have improved outcomes in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and are increasingly incorporated into treatment protocols of Philadelphia chromosome-like (Ph-like, ABL-class) ALL. However, central nervous system (CNS) relapse remains a significant challenge. Imatinib, a first-generation TKI, demonstrates limited CNS penetration in adults, yet data in children are sparse. Methods: This prospective, multicenter study investigated cerebrospinal fluid (CSF) and matched plasma concentrations of imatinib and its primary bioactive metabolite (N-desmethyl-imatinib) in children and young adults with Ph + or Ph-like (ABL-class) ALL. Plasma and CSF samples were analyzed with liquid chromatography tandem mass spectrometry (LC-MS/MS). Linear mixed-effects models were used to assess concentrations across compartments and over time. Results: Between January 2023 and June 2025, 32 paired plasma and CSF samples were collected from ten patients (range 1–8 samples/patient; median: 3). In total, 78% of plasma imatinib concentrations were above 1,000 ng/mL. On average, plasma imatinib concentrations were 189-fold higher than in CSF (geometric mean ratio, 95% CI: 142–249, p < 0.001), which was even more profound for N-desmethyl-imatinib (geometric mean ratio 273, 95% CI: 218–339, p < 0.001). The highest measured CSF-imatinib concentration was 63 ng/mL. During therapy, both plasma and CSF imatinib concentrations declined at an average of 0.32% per day (p < 0.001), resulting in stable CSF-to-plasma ratio over a median follow-up of 5.7 months (range: 0–14 months). Conclusion: The very low CSF concentrations support the rationale for alternative TKIs with improved CNS distribution in patients at risk of CNS relapse. |
| Published |
Springer |
| Type |
Journal article |
| Language |
English |
| Publication date |
2026 |
| CC license |
|
