Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase‐2 study (NordCML006)

Abstract

We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR4.5 was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial

“…The dasatinib arm had more patients achieve BCR-ABL1 ≤ 10% (IS) at 3 months and fewer CML-related deaths (nine of 26 patients v 17 of 26 patients in dasatinib and imatinib arms, respectively). The benefit of dasatinib has been confirmed in additional randomized trials, 26–28 making the data supporting the overall benefit with dasatinib robust.…”

Long‐term follow‐up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic‐phase chronic myeloid leukemia

“…Furthermore, investigators from the DASISION trial reported the ability to maintain the efficacy of dasatinib among patients who had their dose reduced while improving its safety profile . The benefit of dasatinib was demonstrated in additional randomized clinical trials, which further confirmed the overall benefit of dasatinib in treating patients with CML …”

How I treat newly diagnosed chronic myeloid leukemia in 2015

“…Their first-line registration was based on two controlled, company sponsored studies, the DASISION and ENEST trials which enrolled approximately 250 patients in each arm. The published results of the two studies [17,18] are rather similar: the extent of tumor load, as evaluated by Q-PCR (quantitative PCR) for BCR-ABL1, decreased more rapidly in patients treated with the 2nd generation TKIs during the first year; patients on imatinib took approximately double time to reach the same level of molecular remission, although they tended to narrow this gap subsequently [43][44][45] (http://www.medicines.org.uk/emc/medicine/26080).…”

“…While the proportion of patients reaching MMR (or MR 3) tends to become closer over time in patients treated with imatinib or 2nd generation TKIs [43][44][45], 2nd generation TKIs appear superior in reaching deeper responses (MR 4 or MR 4.5) [43,45,61]. Whether these results will translate into a substantially higher proportion of patients who will be able to discontinue their TKIs, it represents a fascinating scientific hypothesis, which however has not been confirmed up to now.…”