Dasatinib Is Associated with Rapid and Durable Complete Hematologic Responses in Patients with Chronic-Phase Chronic Myeloid Leukemia (CPCML).

Achieving a quick and durable complete hematologic response (CHR) is a near-term treatment goal in CP-CML. This is particularly relevant in patients with late CP-CML who are receiving second-line tyrosine kinase inhibitors (TKIs) after failing imatinib therapy. The rapidity of the CHR provides an early assessment of sensitivity or resistance to second-line TKIs and should be used to guide treatment decision in this patient population. In the CA180-013 trial (START-C), 387 subjects resistant to or intolerant of imatinib were treated with dasatinib. At 2 years of follow-up, CHR was achieved in 91% of all subjects (90% of 288 resistant subjects, and 94% of 99 intolerant subjects). Of the 233 patients with abnormal peripheral blood counts at baseline, 203 (87%) achieved CHR (86% imatinib-resistant and 92% imatinib-intolerant). The time to achieve CHR (defined as the duration between the first dose of dasatinib until the first day CHR criteria were met) was rapid, with a median time to CHR of 2.1 weeks (C.I: 2.1 to 2.4) across all cohorts. Furthermore, most subjects who achieved CHR did so within the first two months of treatment. In addition, CHRs achieved with dasatinib were durable; the 12- and 24-month CHR were 92% and 83%, respectively. Moreover, in an optimization trial (CA180-034) comparing efficacy between 100mg and 140mg total dasatinib administered in one or two doses, the rates of, time to, and duration of CHR were comparable to that observed in START-C (Table 1). No difference in time to or duration of CHR was observed between the two schedules. In summary, dasatinib is associated with a rapid and durable CHR in a majority of subjects with CP-CML resistant to or intolerant of imatinib therapy.

Table 1: Percentage of Dasatinib-Treated Patients with CHR who are Imatinib Resistant (CA180-034 trial)