Relationship between trough level of tyrosine kinase inhibitor (imatinib and nilotinib) and BCR-ABL ratios in an Indonesian chronic-phase chronic myeloid leukemia (CML) population

Budi Suprapti; Mareta Rindang Andarsari; Pharmasinta Putri Hapsari; Junaidi Khotib; Suharjono; Siprianus Ugroseno Yudho Bintoro

doi:10.1515/jbcpp-2019-0315

Article

Relationship between trough level of tyrosine kinase inhibitor (imatinib and nilotinib) and BCR-ABL ratios in an Indonesian chronic-phase chronic myeloid leukemia (CML) population

Budi Suprapti , Mareta Rindang Andarsari , Pharmasinta Putri Hapsari , Junaidi Khotib , Suharjono and Siprianus Ugroseno Yudho Bintoro

Published/Copyright: August 4, 2020

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 31 Issue 5

Abstract

Objectives

Among Chronic Myeloid Leukemia (CML) patients treated with Tyrosine Kinase Inhibitor (TKI-imatinib-nilotinib), some showed a suboptimal response. Based on pharmacokinetic studies, TKI trough level (Cmin∞) is associated with clinical outcomes, reflected by the BCR-ABL ratio. However, the interindividual pharmacokinetic variability of imatinib and nilotinib is found to be moderate–high. This study aims to analyze the relationship between TKI Cmin∞ and BCL-ABL ratio in chronic-phase CML patients.

Methods

Cross-sectional study to CML chronic-phase patients treated with imatinib 400 mg daily or nilotinib 400 or 800 mg daily for ≥12 months. The exclusion criteria were therapy discontinuation within 29 days (imatinib) or 8 days (nilotinib) before the sampling day. Blood samples were drawn 1 h before the next dose. Imatinib-nilotinib Cmin∞ and BCR-ABL ratio were measured using HPLC and RT-qPCR. The relationship was analyzed using bivariate correlation Spearman’s rho test.

Results

Twenty-three imatinib and 11 nilotinib patients met the inclusion criteria. The mean imatinib and nilotinib Cmin∞ were 1,065.46 ± 765.71 and 1,445 ± 1,010.35 ng/mL respectively. There were large interindividual variations in both groups (71.87% vs. 69.88%). Half of the patients in each group were found to reach Cmin∞ target (≥1.000 ng/mL, imatinib; ≥800 ng/mL nilotinib), but only 12 (35,29%) of them result in BCR-ABL ratio ≤0.1%. Cmin∞ imatinib was found to be significantly associated with BCR-ABL ratio. But, not with the nilotinib group.

Conclusions

There were high interindividual variations of imatinib and nilotinib correlated with BCR-ABL ratio, but no correlation in nilotinib.

Keywords: BCR-ABL ratio; Cmin∞; CML; imatinib; nilotinib

Corresponding author: Budi Suprapti, Department of Clinical Pharmacy, Airlangga University, Campus C Jalan Mulyorejo, Surabaya, East Java, 60115, Indonesia, E-mail: budi-s@ff.unair.ac.id

Funding source: Minister of Research Technology and Higher Education of Indonesia

Funding source: Tahir Foundation

Acknowledgment

We would like to thank Dr. Soetomo General Hospital for granting permission to use the data provided in this study and the Tahir Foundation.

Research funding: This study was funded by the Minister of Research Technology and Higher Education of Indonesia and the Tahir Foundation.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Conflict of interest: The authors state that they have no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.

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Received: 2019-10-23

Accepted: 2020-04-07

Published Online: 2020-08-04

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2019-0315

Keywords for this article

BCR-ABL ratio; Cmin∞; CML; imatinib; nilotinib