Efficacy of dasatinib in treatment of imatinib-resistant BCR/ABL positive leukemia

Abstract

This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib. 27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph(+) ALL) received 100 - 140 mg/d dasatinib orally. Their overall survival and tolerance were evaluated. The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27 imatinib-resistant BCR/ABL positive leukemia cases, with a median follow-up of 54 (3-75) months. After the dasatinib treatment, 88.8% of all the 27 cases achieved complete hematologic response (CHR), 29.6% of them achieved major cytogenetic response (mCyR), 37% of all achieved complete cytogenetic response (CCyR) and 18.5% cases achieved major molecular response (MMR). Patients who received dasatinib in progress of disease (CML-AP, CML-BC and bone marrow relapse Ph(+) ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph(+) ALL) (P = 0.0377), and 3 - 4 grade adverse events occurred more frequently in progress of disease than that in stable disease. Overall survival of the patients who achieved CCyR after dasatinib therapy was statistically longer than those who did not achieve CCyR (63 m vs 9 m, P = 0.0126). The most common grade 3 - 4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%), neutropenia (48.1%), anemia (33.3%), and non-hematologic events such as pleural effusion (18.5%), pulmonary infection (18.5%), pericardial effusion (11.1%). The 3-4 grade adverse events occurred within 12 months from dasatinib therapy, and were mainly observed in patients with progress of disease. It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients, the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.