Plasma concentrations of dasatinib have a clinical impact on the frequency of dasatinib dose reduction and interruption in chronic myeloid leukemia: an analysis of the DARIA 01 study

• Published in: International journal of clinical oncology Vol. 23; no. 5; pp. 980 - 988
• Main Authors: Mizuta, Shuichi, Sawa, Masashi, Tsurumi, Hisashi, Matsumoto, Kana, Miyao, Kotaro, Hara, Takeshi, Takahashi, Takeshi, Sakemura, Reona, Kojima, Hiroshi, Kohno, Akio, Oba, Mari S., Morita, Satoshi, Sakamoto, Junichi, Emi, Nobuhiko
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01-10-2018; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Body weight; Cancer Research; Chronic myeloid leukemia; Dasatinib - administration & dosage; Dasatinib - blood; Dose-Response Relationship, Drug; Female; Humans; Japan; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Multivariate analysis; Myeloid leukemia; Oncology; Original; Original Article; Patient compliance; Patients; Prospective Studies; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - blood; Surgical Oncology; Survival Rate; Treatment Failure; Young Adult; Dasatinib; Treatment adherence; Individualized dasatinib therapy; Chronic myeloid leukemia; Plasma concentration
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-018-1300-9

Background
Dasatinib has shown promising anti-leukemic activity against chronic myeloid leukemia (CML). However, patients receiving dasatinib frequently require dose reductions and treatment interruptions (treatment alteration).
Methods
We prospectively analyzed the frequency and significance of treatment alteration during dasatinib therapy in patients with CML. In all patients, trough plasma concentrations of dasatinib (
C
min
) at steady state were assessed on day 28 of therapy.
Results
28% of patients had their doses reduced at a median of 42 days, and 25% of patients had temporarily interrupted at a median of 54 days after treatment initiation. The overall dasatinib treatment alteration-free rate at 1 year was 66%. Age was significantly correlated with
C
min
on day 28 (
p
 = 0.014), and the correlation remained significant after adjusting dasatinib dose (g), body weight (kg) (
C
min
/
D
/
W
) (
p
 = 0.026). In the univariate analysis, deep molecular response, advanced PS, higher
C
min
/
D
/
W
were associated with a significantly higher risk of treatment alteration (HR 4.19, 95% CI: 1.06–16.60,
p
 = 0.041; HR 5.26, 95% CI: 1.33–20.80,
p
 = 0.018; and HR 10.15, 95% CI: 2.55–40.48,
p
 = 0.001, respectively). In the multivariate analysis, advanced PS and higher
C
min
/
D
/
W
were correlated with the incidence of treatment alteration (HR 4.78, 95% CI: 1.01–22.70,
p
 = 0.049; HR 6.17, 95% CI: 1.17–32.50, respectively).
Conclusion
Current data demonstrate that patients treated with dasatinib who displayed a high
C
min
/
D
/
W
value and/or advanced PS were at a high risk for altered treatment.