Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients.
J Cancer
; 14(7): 1151-1156, 2023.
Article
em En
| MEDLINE
| ID: mdl-37215448
ABSTRACT
Infiltration of malignant cells into the central nervous system in hematological malignancies correlates with poor clinical outcomes. Investigations into the penetration of venetoclax into the central nervous system have been limited. We report venetoclax pharmacokinetics in plasma and cerebrospinal fluid samples from a Phase 1 study in pediatric patients with relapsed or refractory malignancies that demonstrate venetoclax ability to cross into the central nervous system. Venetoclax was detected in cerebrospinal fluid (CSF) samples, with concentrations ranging from < 0.1 to 26 ng/mL (mean, 3.6 ng/mL) and a plasmaCSF ratio ranging from 44 to 1559 (mean, 385). PlasmaCSF ratios were comparable among patients with AML and ALL and no clear trend was observed in the ratios over the course of treatment. Moreover, improvement in central nervous system (CNS) involvement status was observed in patients who had measurable concentrations of venetoclax in the CSF. CNS resolution was observed for up to six months while on treatment. These findings highlight the potential role of venetoclax and provide the opportunity to further investigate its utility in improving clinical outcomes for patients with CNS complications.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
J Cancer
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos