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
| Main Authors: | Budi Suprapti, Mareta Rindang Andarsari, Pharmasinta Putri Hapsari, Junaidi Khotib, Suharjono, Siprianus Ugroseno Yudho Bintoro |
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| Format: | Article PeerReviewed Book |
| Bahasa: | eng |
| Terbitan: |
Walter de Gruyter GmbH
, 2020
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| Subjects: | |
| Online Access: |
http://repository.unair.ac.id/100831/3/Artikel%20C-04%20%2B%20Koresponden.pdf http://repository.unair.ac.id/100831/2/Validasi%20C-04.pdf http://repository.unair.ac.id/100831/1/C-04%20Result.pdf http://repository.unair.ac.id/100831/ https://www.degruyter.com/view/journals/jbcpp/31/5/article-20190315.xml https://doi.org/10.1515/jbcpp-2019-0315 |
Daftar Isi:
- 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 (C∞min) 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 C∞min 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 C∞min 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 C∞min 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 C∞min target (≥1.000 ng/mL, imatinib; ≥800 ng/mL nilotinib), but only 12 (35,29%) of them result in BCR-ABL ratio ≤0.1%. C∞min 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.