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Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following
A Hochhaus1, M C Müller, J Radich
1III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany. andreas.hochhaus@med.uni-jena.de
Abstract:
Dasatinib is a highly potent BCR-ABL inhibitor that has shown durable efficacy in patients with chronic phase (CP) chronic myeloid leukemia (CML) after resistance, suboptimal response, or intolerance to prior imatinib. In patients with CML, BCR-ABL transcript measurement is the most sensitive method for assessing minimal residual disease. Here, molecular responses were analyzed in 1067 patients with CML-CP treated with dasatinib during phase II/III trials. After 3, 6, 12, and 24 months of follow-up, a major molecular response (MMR) was achieved by 12, 22, 35, and 40% of patients, respectively. The 24-month MMR rate was 34% in patients with resistance or suboptimal response to imatinib (n=829) and 63% in imatinib-intolerant patients (n=238). Among patients who had achieved a complete cytogenetic response (CCyR), 72% also achieved MMR. Responses with dasatinib 100 mg once daily were similar to other doses. In landmark analyses, 24-month progression-free survival was higher in patients who had achieved MMR or CCyR at 12 months than in those without MMR or CCyR at 12 months. MMR at 12 months was associated with a longer duration of CCyR. Overall, this analysis shows that dasatinib treatment results in high MMR rates in patients with CML-CP after imatinib failure.
Insights
Dasatinib effectively treats chronic myeloid leukemia (CML) in patients resistant to imatinib. High rates of major molecular response (MMR) were observed, indicating significant disease control.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Dasatinib is a potent BCR-ABL inhibitor for chronic myeloid leukemia (CML).
- BCR-ABL transcript measurement assesses minimal residual disease in CML.
- Imatinib is a prior treatment for CML, with resistance, suboptimal response, or intolerance being common challenges.
Purpose of the Study:
- To analyze molecular responses in CML patients treated with dasatinib after imatinib failure.
- To evaluate the efficacy of dasatinib in achieving major molecular response (MMR).
Main Methods:
- Analysis of molecular responses in 1067 CML patients from phase II/III trials of dasatinib.
- Assessment of MMR rates at 3, 6, 12, and 24 months.
- Comparison of MMR rates in imatinib-resistant/intolerant subgroups.
Main Results:
- MMR rates at 24 months were 40% overall, 34% in imatinib-resistant/suboptimal response, and 63% in imatinib-intolerant patients.
- 72% of patients achieving complete cytogenetic response (CCyR) also achieved MMR.
- Achieving MMR or CCyR at 12 months correlated with higher 24-month progression-free survival and longer CCyR duration.
Conclusions:
- Dasatinib treatment leads to high MMR rates in CML patients post-imatinib failure.
- Early molecular response with dasatinib is associated with improved long-term outcomes.
- Dasatinib demonstrates durable efficacy in managing CML after prior imatinib therapy.
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