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).
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 (Cmin) at steady state were assessed on day 28 of therapy.
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 Cmin on day 28 (p = 0.014), and the correlation remained significant after adjusting dasatinib dose (g), body weight (kg) (Cmin/D/W) (p = 0.026). In the univariate analysis, deep molecular response, advanced PS, higher Cmin/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 Cmin/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).
Current data demonstrate that patients treated with dasatinib who displayed a high Cmin/D/W value and/or advanced PS were at a high risk for altered treatment.
Hughes T, Deininger M, Hochhaus A et al (2006) Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108:28–37 CrossRefPubMedPubMedCentral
De Francia S, D’Avolio A, De Martino F et al (2009) New HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib, and nilotinib in human plasma. J Chromatogr B Anal Technol Biomed Life Sci 877:1721–1726 CrossRef
Rousselot P, Mollica L, Guerci-Bresler A et al (2014) Dasatinib daily dose optimization based on residual drug levels resulted in reduced risk of pleural effusions and high molecular response rates: final results of the randomized OPTIM dasatinib Trial. Abstract ABSSUB-5297, Congress of the European Hematology Association (EHA)
- 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
Mari S. Oba
- Springer Japan
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