RT info:eu-repo/semantics/article
T1 Pharmacogenetic Biomarkers of Ibrutinib Response and Toxicity in Chronic Lymphocytic Leukemia: Insights from an Observational Study
A1 Pérez-Gómez, Noelia
A1 Sanz-Solas, Antonio
A1 Cuevas, Beatriz
A1 Cuevas, María Victoria
A1 Alonso-Madrigal, Cristina
A1 Loscertales, Javier
A1 Álvarez-Nuño, Rodolfo
A1 García, Covadonga
A1 Zubiaur, Pablo
A1 Villapalos-García, Gonzalo
A1 Parra-Garcés, Raúl Miguel
A1 Mejía-Abril, Gina
A1 Alcaraz, Raquel
A1 Vinuesa, Raquel
A1 Díaz-Gálvez, Francisco Javier
A1 González-Oter, María
A1 García-Sancha, Natalia
A1 Azibeiro-Melchor, Raúl
A1 González-López, Tomás José
A1 Abad-Santos, Francisco
A1 Labrador, Jorge
A1 Saiz-Rodríguez, Miriam
K1 Chronic lymphocytic leukemia
K1 Ibrutinib
K1 Pharmacogenetics
K1 Polymorphisms
K1 Leucemia linfática crónica-Tratamiento
K1 Chronic lymphocytic leukemia-Treatment
AB Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitativepolymerase chain reaction (qPCR) using a ViiA7® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming touncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity.
PB MDPI
SN 1424-8247
YR 2025
FD 2025-07
LK https://hdl.handle.net/10259/11908
UL https://hdl.handle.net/10259/11908
LA eng
NO Project financed by the Regional Health Management of Castilla y León (GRS 2202/A/2020). M.S.R. research was supported by Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, through the Sara Borrell Program (CD21/00022). A.S.S.’s contract was funded by Fundación hna, 2nd edition of the Scientific Health Research Award. G.V.G was co-financed by ISCIII and the European Social Fund (PFIS predoctoral grant, number FI20/00090).
DS Repositorio Institucional de la Universidad de Burgos
RD 11-jul-2026