Can dasatinib be used in patients with accelerated or blast phase CML?

Dasatinib is a potent second-generation BCR-ABL tyrosine kinase inhibitor (TKI) initially approved for the treatment of chronic phase chronic myeloid leukemia (CML) and patients who are resistant or intolerant to imatinib. With an in-depth understanding of its pharmacological mechanism and clinical manifestations, its indications have gradually expanded to the more challenging accelerated phase and blast phase (i.e., acute transformation phase) of CML, especially those patients who have poor response to previous treatment regimens. After CML progresses to the accelerated phase or blast phase, the malignancy of the disease is significantly enhanced, and the expression and activity of BCR-ABL fusion protein are significantly increased, making the disease more resistant to standard treatments. At this time, traditional TKIs such as imatinib are often difficult to maintain effective disease control. Dasatinib, with its stronger affinity and broader kinase inhibitory spectrum, clinically shows a higher response rate and faster response onset time than imatinib, making it one of the important treatment options for patients with accelerated phase and blast crisis CML.

Dasatinib not only has a strong inhibitory effect onBCR-ABL, but also inhibits a variety of other tyrosine kinases, such as SRC family kinases, c-KIT, PDGFR, etc., which makes it exhibit stronger biological activity in controlling disease progression and delaying the clonal evolution of leukemia cells. For patients with accelerated-stage CML, the use of dasatinib can often quickly induce hematological and cytogenetic remission, thereby winning a longer disease control period for the patient and even creating conditions for allogeneic hematopoietic stem cell transplantation. Especially in blast phase CML patients, the combination treatment strategy of dasatinib has gradually become a research hotspot, such as combined with chemotherapy, in an attempt to eliminate Ph+ leukemia clones while relieving symptoms and prolonging overall survival. It should be noted that in the treatment of blast phase CML, patients' conditions are often more complex and their tolerance to drugs is poor. Therefore, the dose management, safety monitoring and individualized dosing strategy of dasatinib are particularly important.

Dasatinib is also approved for the treatment of Ph+ acute lymphoblastic leukemia (Ph+ ALL), particularly in patients who are resistant to imatinib or other chemotherapy regimens. Due to the rapid progression and poor prognosis of Ph+ALL, traditional chemotherapy methods often fail to achieve long-term remission. However, dasatinib has shown the potential to improve disease-free survival and overall survival when used in combination with chemotherapy. In addition, its use in pediatric patients has gradually gained recognition, and it is suitable for children 1 year old and above, newly treated or relapsed chronic phase Ph+CML, and newly diagnosed Ph+ALL, marking its increasing status in the treatment of pediatric leukemia.

In general, dasatinib is not only effective in the chronic phaseIt occupies an important position in CML and shows unique therapeutic advantages in patients with accelerated phase and blast crisis CML. Through strong inhibition of BCR-ABL mutations and broad-spectrum effects on multiple pathogenic kinases, it provides a feasible treatment option for patients with high-risk CML. However, during use, it is still necessary to develop an individualized treatment plan based on the patient's specific situation, disease progression, previous treatment history, drug tolerance and other factors. In addition, for some mutated BCR-ABL (such as T315I mutation), the activity of dasatinib may still be limited. At this time, alternative treatments such as third-generation TKIs such as Ponatinib may need to be considered.

Reference materials:https://go.drugbank.com/drugs/DB01254