Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase

• DOI: 10.1038/leu.2008.221
• Publication Date: 2008-08-28T09:48:50Z
• Authors: J Cortes; D-W Kim; E Raffoux; G Martinelli; E Ritchie; L Roy; S Coutre; S Corm; N Hamerschlak; J-L Tang; A Hochhaus; H J Khoury; T H Brümmendorf; M Michallet; G Rege-Cambrin; C Gambacorti-Pass...; J P Radich; T Ernst; C Zhu; J M A Van Tornout; M Talpaz
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; Dasatinib; Administration, Oral; Antineoplastic Agents; Genes, abl; Disease-Free Survival; 03 medical and health sciences; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Humans; Aged; Aged, 80 and over; Hematopoietic Stem Cell Transplantation; Middle Aged; Combined Modality Therapy; 3. Good health; Treatment Outcome; Male; Adolescent; Aged, 80 and over; Thiazoles; Young Adult; Middle Aged; Genes, abl; Hematopoietic Stem Cell Transplantation; Female; Pyrimidines; Protein Kinase Inhibitors; Disease-Free Survival; Piperazines; Blast Crisis; Humans; Antineoplastic Agents; Administration, Oral; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug Resistance, Neoplasm; Aged; Adult; Combined Modality Therapy; Drug Resistance, Neoplasm; MYELOID LEUKEMIA; IMATINIB; DASATINIB; Benzamides; Imatinib Mesylate; Female; Blast Crisis

Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in <or=6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.