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Capillary Sampling Enables Venetoclax Concentration Measurement in Acute Myeloid Leukaemia Within Academic Multicentre Trial




TekijätKytölä, Sari; Kurkela, Mika; Kiiski, Johanna I.; Vänttinen, Ida; Ruokoranta, Tanja; Partanen, Anu; Holopainen, Annasofia; Pyörälä, Marja; Kuusisto, Milla E. L.; Siitonen, Timo; Koskela, Sirpa; Rimpiläinen, Johanna; Ettala, Pia; Kuusanmäki, Heikki; Niemi, Mikko; Backman, Janne T.; Kontro, Mika

KustantajaWILEY

KustannuspaikkaHOBOKEN

Julkaisuvuosi2025

JournalBasic and Clinical Pharmacology and Toxicology

Tietokannassa oleva lehden nimiBASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

Lehden akronyymiBASIC CLIN PHARMACOL

Artikkelin numeroe70041

Vuosikerta136

Numero6

Sivujen määrä11

ISSN1742-7835

eISSN1742-7843

DOIhttps://doi.org/10.1111/bcpt.70041

Verkko-osoitehttps://doi.org/10.1111/bcpt.70041


Tiivistelmä
Venetoclax has improved outcomes for acute myeloid leukaemia (AML) patients unfit for intensive chemotherapy. Managing cytopenias and infections remains challenging. Previous pharmacokinetic studies have shown considerable variability in venetoclax concentrations between individuals; however, data regarding whether higher levels increase toxicity or impact efficacy are limited. This study assessed the feasibility of using fingertip capillary blood plasma, collected via microsampling, to measure venetoclax trough concentrations and explored their association with toxicity and treatment outcomes. Concentrations were measured during the first two therapy cycles in 89 patients with newly diagnosed or relapsed or refractory AML receiving azacitidine and venetoclax. Validation with 37 parallel venipuncture and capillary samples showed excellent correlation (R-2 of 0.835, p < 0.0001). No significant associations were found between venetoclax concentrations and patient characteristics such as gender, age and weight. While no statistically significant effects on therapy outcomes or adverse events were identified, trends suggested lower concentrations in refractory patients and higher in those with morphologic leukaemia free state or extended cycle length. Additionally, three separate CYP3A4 and CYP3A5 single-nucleotide polymorphisms were analysed in 81 patients for their potential impact on venetoclax concentrations. This study demonstrates that the capillary blood plasma method is viable for measuring venetoclax levels.


Julkaisussa olevat rahoitustiedot
This work was supported by Helsinki University: iCAN - Digital Precision Medicine and HiLIFE, FiCAN South, Finnish Medical Foundation, Cancer Foundation Finland, and Helsinki University Hospital Comprehensive Cancer Center.


Last updated on 2025-13-06 at 08:30