Utility of therapeutic drug monitoring of venetoclax in acute myeloid leukemia

被引:13
作者
Kobayashi, Masayuki [1 ,2 ]
Yasu, Takeo [2 ,3 ]
Suzaki, Ken [1 ]
Kosugi, Nobuharu [1 ]
机构
[1] Tokyo Metropolitan Bokutoh Hosp, Dept Hematol, Sumida Ku, 4-23-15 Kotobashi, Tokyo 1308575, Japan
[2] Bokutoh Hosp Meiji Pharmaceut Univ Joint Res Ctr, Sumida Ku, Tokyo, Japan
[3] Meiji Pharmaceut Univ, Pharmaceut Educ & Res Ctr, Dept Med Therapy Res, Kiyose, Japan
关键词
Therapeutic drug monitoring; Venetoclax; Acute Myeloid Leukemia; AML; AZACITIDINE;
D O I
10.1007/s12032-022-01865-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The favorable outcomes of venetoclax-based regimens in older adults with acute myeloid leukemia (AML) may result in its regimen becoming the standard treatment. However, the dosage of venetoclax is fixed, irrespective of body surface area (BSA) or weight. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help optimize treatment in a safe and effective manner. Twelve patients with AML who received venetoclax-based treatment were enrolled in this study. Blood samples were collected before venetoclax administration, and the minimum plasma concentration (Cmin) was evaluated. The concentration of venetoclax was evaluated using a simple, sensitive, and cost-effective assay using high-performance liquid chromatography, as described previously. The median age was 74 (70-85) years. Ten patients received venetoclax in combination with azacitidine and one patient received low-dose cytarabine (LDAC). The patients BSA ranged from 1.345 to 1.912 m2 (median 1.543). The dose of venetoclax was 400 mg with azacitidine, and 600 mg with LDAC. In four patients who were taking CYP3A4 inhibitors, venetoclax was reduced to 50 mg according to the prescribing information. The Cmin ranged from 0.39 to 2.49, and the patient taking itraconazole showed highest Cmin regardless of the reduction of venetoclax. Most patients showed higher Cmin compared to the data from previous clinical trials, and BSA and venetoclax concentrations showed a negative correlation. Many Asian AML patients > 75 years old are petite and receive CYP3A4 inhibitors. Therefore, the TDM of venetoclax may be useful.
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页数:5
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