Efficacy
A MaHR was achieved by 22 (55%) and 19 (43%) patients in the once- and twice-daily dasatinib monotherapy groups, respectively. MCyR was seen in 28 (70%) and 23 (52%) patients, without significant difference between the two groups.r
The median PFS was 4.0 months in the once-daily group and 3.1 months in the twice-daily group (p=0.735). The median OS was 6.5 months in the once-daily group and 9.1 months in the twice-daily group (p=0.336). There were no significant differences in outcomes between either once- or twice-daily dosing. Only 2 patients in the once-daily group and 3 patients in the twice-daily group were still on therapy at 2-year follow-up, though 5 patients discontinued in order to proceed to transplant.r
There did not appear to be a difference in outcome between those patients who failed imatinib due to resistance and those who experienced imatinib intolerance. The three patients with T315I mutation detected had no objective response to dasatinib, as would be expected.r
Between September 2006 and March 2012, 72 Ph+ ALL patients, with a median age of 55 years (range 21-80) were treated upfront with dasatinib and hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper CVAD).r With a median follow up of 67 months (range 33-97), 33 patients (46%) were alive and 30 (43%) remained in first complete remission (CR1). Patients younger than 40 years benefited from allograft following achievement of CR1, but those older than 40 years did not appear to benefit, with the caveat of small numbers.
Dasatinib is continued indefinitely in the majority of Ph+ ALL protocols after completion of chemotherapy unless unacceptable toxicities occur.