Contributions
Abstract: PB1938
Type: Publication Only
Background
A fixed dosing regimen of BCR-ABL1 tyrosine kinase inhibitors (TKIs) can lead to under- and over-exposure to the drug in heavy and light-weight patients, respectively.
Aims
The aim of this analysis is to assess the effects of the body surface area(BSA)-adjusted doses of dasatinib on molecular responses (MRs) and dose-limiting toxicities (DLTs) in patients with chronic myeloid leukemia (CML).
Methods
A clinical study was conducted in newly diagnosed adult patients with CML in chronic phase (CP-CML). After adjusting the dose using each patient’s body surface area (Dose/BSA), the effects of Dose/BSA were evaluated on the achievement of MRs and the occurrence of DLTs. The MRs were the MR2 defined as BCR-ABL1 transcript < 1% on the international scale (IS) at 6 months, equevalent to the complete cytogenetic response, and the major molecular response (MMR) defined as the transcript < 0.1% IS at 12 months of dasatinib treatment. A DLT was defined as an interruption or reduction of dasatinib dose owing to any grade 3+ adverse reaction associated with dasatinib treatment by 12 months. Logistic regression analyses were performed to determine the association between the Dose/BSA and the achievement of MRs or the occurrence of DLTs. Chi-square tests were used to compare the MRs and DLTs between the patients divided into quartile groups of Dose/BSA.
Results
The clinical data were collected from all 101 patients enrolled in the study between the year of 2013 and 2017. They were receiving a fixed initial dose of dasatinib 100 mg once daily. The higher the Dose/BSA of dasatinib, the lower the degree of MR achievement was. The rates of MR2 and MMR achievement were 80% and 66%, respectively. The higher Dose/BSA was associated with the lower achievement of MR2 (logit [P] = - 0.085 × [Dose/BSA] + 6.61, p = 0.024). Regarding DLTs, the rate of DLT occurrence was 46%. The higher the Dose/BSA of dasatinib, the greater the occurrence of DLTs was (logit [P] = - 0.12 × [Dose/BSA] - 7.20, p < 0.001). From the first to the fourth quartile groups of Dose/BSA, the rates of MR2 achievement were 84, 92, 76 and 65%, respectively, which demonstrated a decreasing trend as Dose/BSA increases (chi-square test, p = 0.016). In addition, the rates of DLT occurrence from the first to the fourth quartile groups of Dose/BSA were 13, 39, 76 and 59%, respectively, which demonstrated an increasing trend as Dose/BSA increases (chi-square test, p < 0.001).
Conclusion
The higher Dose/BSA of dasatinib not only increased the chance of DLT occurrence but also decreased the probability of MR achievement. It appears necessary to administer a lower initial dose of dasatinib to an individual patient in order to achieve a higher MR as well as to keep a lower rate of DLTs in the treatment of patients with CP-CML.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular response, toxicity, Tyrosine kinase inhibitor
Abstract: PB1938
Type: Publication Only
Background
A fixed dosing regimen of BCR-ABL1 tyrosine kinase inhibitors (TKIs) can lead to under- and over-exposure to the drug in heavy and light-weight patients, respectively.
Aims
The aim of this analysis is to assess the effects of the body surface area(BSA)-adjusted doses of dasatinib on molecular responses (MRs) and dose-limiting toxicities (DLTs) in patients with chronic myeloid leukemia (CML).
Methods
A clinical study was conducted in newly diagnosed adult patients with CML in chronic phase (CP-CML). After adjusting the dose using each patient’s body surface area (Dose/BSA), the effects of Dose/BSA were evaluated on the achievement of MRs and the occurrence of DLTs. The MRs were the MR2 defined as BCR-ABL1 transcript < 1% on the international scale (IS) at 6 months, equevalent to the complete cytogenetic response, and the major molecular response (MMR) defined as the transcript < 0.1% IS at 12 months of dasatinib treatment. A DLT was defined as an interruption or reduction of dasatinib dose owing to any grade 3+ adverse reaction associated with dasatinib treatment by 12 months. Logistic regression analyses were performed to determine the association between the Dose/BSA and the achievement of MRs or the occurrence of DLTs. Chi-square tests were used to compare the MRs and DLTs between the patients divided into quartile groups of Dose/BSA.
Results
The clinical data were collected from all 101 patients enrolled in the study between the year of 2013 and 2017. They were receiving a fixed initial dose of dasatinib 100 mg once daily. The higher the Dose/BSA of dasatinib, the lower the degree of MR achievement was. The rates of MR2 and MMR achievement were 80% and 66%, respectively. The higher Dose/BSA was associated with the lower achievement of MR2 (logit [P] = - 0.085 × [Dose/BSA] + 6.61, p = 0.024). Regarding DLTs, the rate of DLT occurrence was 46%. The higher the Dose/BSA of dasatinib, the greater the occurrence of DLTs was (logit [P] = - 0.12 × [Dose/BSA] - 7.20, p < 0.001). From the first to the fourth quartile groups of Dose/BSA, the rates of MR2 achievement were 84, 92, 76 and 65%, respectively, which demonstrated a decreasing trend as Dose/BSA increases (chi-square test, p = 0.016). In addition, the rates of DLT occurrence from the first to the fourth quartile groups of Dose/BSA were 13, 39, 76 and 59%, respectively, which demonstrated an increasing trend as Dose/BSA increases (chi-square test, p < 0.001).
Conclusion
The higher Dose/BSA of dasatinib not only increased the chance of DLT occurrence but also decreased the probability of MR achievement. It appears necessary to administer a lower initial dose of dasatinib to an individual patient in order to achieve a higher MR as well as to keep a lower rate of DLTs in the treatment of patients with CP-CML.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular response, toxicity, Tyrosine kinase inhibitor