Serial evaluation of the pharmacokinetics of ponatinib in patients with CML and Ph + ALL
Serial evaluation of the pharmacokinetics of ponatinib in patients with CML and Ph + ALL
复制标题
普纳替尼在 CML 和 Ph ALL 患者中药代动力学的系列评估
DOI：
10.1007/s12185-021-03186-8
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Takahashi N.
中科院分区：
文献类型：
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作者：
Kawano N;Kimura S;Miura M;Tochigi T;Nakaike T;Yamashita K;Mashiba K;Kikuchi I;Takahashi N.
虽然酪氨酸激酶抑制剂（TKI）在慢性髓性白血病（CML）和费城染色体阳性急性淋巴细胞白血病（Ph + ALL）的治疗中发挥着至关重要的作用，但对TKI的不耐受和耐药性一直是严重的问题。由于缺乏研究，TKI药代动力学（PK）的重要性目前尚不清楚。我们检查了第三代TKI泊那替尼的PK，以监测1例CML慢性期（CP-CML）患者和2例接受异基因造血干细胞移植（allo-HSCT）的患者（1例CML急变（BC-CML）和1例Ph + ALL）治疗期间的副作用和疗效。CP-CML患者对多种TKI（达沙替尼、尼洛替尼、伊马替尼和博舒替尼）不耐受，因此转换为泊那替尼（15 mg/天）。接受allo-HSCT治疗BC-CML和Ph + ALL的患者接受泊那替尼（15 mg/天）作为维持治疗。值得注意的是，泊那替尼PK的系列评价显示，患者1、2和3的中位谷值（ng/ml）分别为17. 2（12. 2 - 34. 5）、33. 1（21. 2 - 40. 3）和27. 7（13. 6 - 29. 9）。这些值在目标浓度（23 ng/ml）附近。所有患者均保持完全缓解，无副作用。总之，泊那替尼PK的系列评价可能会产生有关其安全性和疗效的有意义的信息。
Although tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL), intolerance and resistance to TKIs have been serious problems. Due to a lack of research, the importance of the pharmacokinetics (PK) of TKIs is currently unclear. We examined the PK of the third-generation TKI ponatinib to monitor side effects and efficacy during treatments for one patient with CML-chronic phase (CP-CML) and two who received allogeneic hematopoietic stem cell transplantation (allo-HSCT), one for CML-blastic crisis (BC-CML) and one for Ph + ALL. The patient with CP-CML was intolerant to multiple TKIs (dasatinib, nilotinib, imatinib, and bosutinib) and thus was switched to ponatinib (15 mg/day). The patients who received allo-HSCT for BC-CML and Ph + ALL received ponatinib (15 mg/day) as maintenance therapy. Notably, serial evaluation of the PK of ponatinib showed that the median trough values (ng/ml) were 17.2 (12.2–34.5), 33.1 (21.2–40.3) and 27.7 (13.6–29.9) in patients 1, 2, and 3, respectively. These values were around the target concentration (23 ng/ml). All patients are maintaining complete remission without side effects. In conclusion, serial evaluation of PK of ponatinib may yield meaningful information about its safety and efficacy.