Do I have to take dasatinib permanently to maintain efficacy?

Dasatinib (Dasatinib), as an oral second-generation TKI for the treatment of chronic phase chronic myeloid leukemia (CP+CML), has been widely used in adult and pediatric patients. But there are still many questions about whether it needs to be continued for life after a specific therapeutic response is achieved.

In clinical studies, dasatinib treatment is often continued until disease progression or patients cannot tolerate it. At this time, we do not know exactly how discontinuing treatment after achieving cytogenetic response (eg, complete cytogenetic response [CCyR]) or major molecular response (MMR and MR4.5) will affect a patient's long-term disease status. Of note, the longest documented treatment duration with dasatinib in pediatric patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) was 2 years.

The in vitro inhibitory effect of dasatinib is far greater than that of imatinib, and its inhibitory potency against unmutatedBCR-ABL1 kinase is 325 times greater than that of the latter. In addition, it also has inhibitory effects on the Src kinase family, which may be particularly important in regulating certain key cell signaling pathways. Dasatinib was initially mainly used for patients with poor response to treatment. Later, it was compared with imatinib and was finally approved as a first-line CML treatment.

Long-term clinical trial follow-up data show that dasatinib can induce faster and deeper therapeutic responses at an earlier time point than imatinib. The proportion of patients receiving dasatinib treatment who achieved BCR-ABL1 transcript (IS) ≤10% at 3 months was significantly higher than that in the imatinib group. Those patients who met treatment criteria within 3 months had a correspondingly higher proportion of complete cytogenetic response, major molecular response, and deeper molecular response within 5 years.