Efficacy and SAFETY of Dasatinib 50 MG Once Daily DOSE In PATIENTS with CHRONIC PHASE CML WHO Failed IMATINIB

Dasatinib is multi-targeted kinase inhibitor and it is approved therapy for patients with imatinib-resistant or imatinib-intolerant CML or newly diagnosed CML (chronic phase). The recommended dosing regimen is Dasatinib 100 mg once daily (QD), based on results from the CA180-034 dose-optimization study in patients with CML-CP and resistance or intolerance to prior therapy and it is active against the vast majority of BCR/ABL mutations apart from T315I and can overcome emerging resistance.

to assess the efficacy and safety of 50 mg once daily dose of Dasatinib in achieving complete hematological remission (CHR),complete cytogenetic remission(CCYR) and major molecular response (MMR) in patients with CML-CP and resistance or intolerance to prior imatinib therapy.

nine adult patients (aged ≥18 years) with prior imatinib failure were enrolled in this study after informed consent, between September and November 2009 and followed for 18 months. Received Dasatinib 50 mg once daily as second line therapy and were evaluated at baseline,3,6, 12, and 18 months as per European leukemia net(ELN) guidelines for response CHR, CCYR, MMR mutation analysis was not done because it is not available in our centre. Patients with baseline pleural effusion or ejection fraction less than 50% were excluded. Chest x-rays were performed at baseline and at 6 months, or more frequently if indicated clinically. Pleural effusions were graded according to CTCAE v3.0 criteria: grade 1, asymptomatic; grade 2, symptomatic, ≤ 2 therapeutic thoracenteses; grade 3, symptomatic requiring supplemental oxygen, > 2 therapeutic thoracenteses; grade 4, life-threatening, hemodynamic instability.

All patients achieved complete hematological as well as complete cytogenic response within three months and remains so at 6 and 12 months assessment, 18 months assessment for molecular response showed that 8 out of 9 achieved major molecular response and one patient achieved complete molecular response, grade two or more toxicity were not seen in any patient. Anemia and neutropenia Grade ≥ 2 were not observed in any patient, thrombocytopenia grade one was observed in one patient. Non-hematologic adverse drug reactions like fluid retention; including pleural effusion, nausea vomiting, myalgia, muscle inflammation and rash were not observed in any patient.

In patients with chronic phase chronic myeloid leukemia who failed first generation TKI (Imatinib). Dasatinib 50 mg once daily is safe, effective and capable of achieving complete hematological and cytogenetic remissions well as major molecular response‘ with better toxicity profile keeping in consideration the small number of patient’s further studies are needed to confirm this result.

No relevant conflicts of interest to declare.