Efficacy and Safety of Dasatinib in Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) with Imatinib Resistance or Intolerance

Dasatinib is highly potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib and a 16-fold higher potency than nilotinib in vitro. Across a series of phase II and III trials with more than 2 years of follow-up, dasatinib has demonstrated durable efficacy in patients with CML following resistance or intolerance to imatinib. We conducted a phase II study to evaluate the efficacy and safety of dasatinib in patients with imatinib resistance or intolerance in the Japanese population.

54 CML- CP patients (median age 63.5 years) with resistance, intolerance or a suboptimal response to imatinib were submitted to dasatinib 100mg once daily. Efficacy and safety were assessed using rates of major molecular response (MMR)/ complete molecular response (CMR) or drug-related adverse events (AEs) respectively. All analyses were based on the intension-treat principle.

Until now, the results of 32 patients, who passed more than 12 months, have been analysed. The median time since of prior imatinib therapy was 19.2 months with 57.4 % being imatinib-resistant and 42.6 % imatinib-intolerant. The incidence of MMR (primary endopoint) and complete molecular response at 12 months was 59.3 % (95% confidence interval, 45.0 – 72.4 %), and 24.1 % patients, respectively. Progression to the accelerated or blastic phase had not been observed. All patients with baseline samples tested for mutations, and different mutations were not observed. Non-hematological AEs were mostly grade 1/2. Grade 3/4 non-hematological AEs were infrequent, including increased AST (1.9%), and increased creatinine (1.9%), respectively. Grade 1/2 fluid retention adverse events were shown in 10 patients, including 2 patients with edema, and 9 patients with pleural effusion. Grade 3/4 hematological toxicities including anemia (1.9%), neutropenia (14.8%), and thrombocytopenia (9.3 %) were shown, and 13 patients have permanently discontinued treatment due to adverse effects.

Dasatinib treatment results in high rate of molecular response in CML-CP patients with resistance or intolerance to imatinib, and approximately 60% of evaluated patients who switched to dasatinib achieved MMR at 12 months. Importantly, among all patients who achieved molecular response, 24.1 % patients achieved CMR. Dasatinib at a dose of 100 mg once daily was generally well-tolerated, and had better efficacy for patients with CML-CP post imatinib failure.

No relevant conflicts of interest to declare.