New hope for chronic myelogenous leukemia patients: dasatinib offers better efficacy with shorter treatment

Abstract

Although the discovery of tyrosine kinase inhibitors (TKIs) has dramatically improved the prognoses of chronic myelogenous leukemia (CML) patients, a cure has remained elusive. Unanswered questions include how long must a patient continue on TKI therapy, and how does a patient know when he/she can safely stop or finish this therapy? Imagawa et al. have carefully addressed these questions of safety and efficacy using a stop study of the second-generation TKI dasatinib. The results of a multicenter phase II trial termed the "dasatinib discontinuation" (DADI) trial indicated that 48% (30/63) of CML patients who had maintained a deep molecular response (DMR) to second-line or subsequent dasatinib therapy for at least for 1 year did not show any signs of disease relapse. Thus, even after it is stopped, dasatinib treatment may decrease the chance of disease relapse and provide a curative benefit to CML patients. This work by Imagawa et al. strongly supports the clinical utility of the second-generation TKI dasatinib for CML treatment.

Keywords: Chronic myelogenous leukemia (CML); dasatinib discontinuation (DADI); deep molecular response (DMR); tyrosine kinase inhibitor (TKI) therapy.

Figure 1

Model of mechanisms by which dasatinib might prevent CML relapse. Relapse of CML disease in the form of the generation of new CML cells is due to the survival of CML stem cells, which are insensitive to TKIs. The second-generation TKI dasatinib may have more than one beneficial effect. In addition to direct inhibition of kinase activities, which may include enzymes other than ABL1 kinase, dasatinib may have off-target effects that eliminate CML stem cells and/or CML cells. Dasatinib also appears to increase the number of NK cells and to reduce the number of Treg cells in CML patients. These impacts on the immune system may help to suppress CML stem cells long after dasatinib has been discontinued.