Five-year follow-up of patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib.

Abstract

6512 Background: Dasatinib, a potent BCR-ABL inhibitor, is indicated as a second-line therapy for patients (pts) with imatinib-resistant or -intolerant CML. This 5-year (yr) analysis is the longest follow-up of CML-CP pts treated with a second-generation BCR-ABL inhibitor. Methods: Study design and endpoints have been described previously (Shah 2008, J Clin Oncol). Pts (N=670) were randomized to dasatinib: 100 mg once daily (QD), 50 mg twice daily (BID), 140 mg QD, or 70 mg BID. Results: Results herein are based on 4-yr data; 5-yr data will be presented. After 4 yrs minimum follow-up, 251 (37%) pts remain on treatment. More pts remain on treatment in the dasatinib 100 mg QD arm (n=74) compared with all other arms. Efficacy data for pts randomized to 100 mg QD (n=167) are: 66% progression-free survival (PFS), 82% overall survival (OS), and 4% transformation to advanced disease. In a landmark analysis of dasatinib 100 mg QD, achievement of complete cytogenetic response (CCyR with or without major molecular response) at 12 months (mos) is associated with an 87% PFS, and achievement of a partial CyR is associated with 78% PFS compared with PFS of 45% for pts with other/no CyR. For dasatinib 100 mg QD, non-hematologic adverse events (AEs; all grades) generally first occur <24 mos and cumulatively include: headache (33%), diarrhea (28%), fatigue (25%), and pleural effusion (24%); and hematologic AEs (grades 3/4) generally occur <12 mos: neutropenia (36%) and thrombocytopenia (24%). Dose/schedule modifications were permitted to manage AEs. Analysis of dosing by last dose available demonstrates that, across the 4 arms, 178 (71%) pts were on QD dosing, of which 107 (60%) pts were on ≥100 mg QD. Switching from BID to QD dosing occurred in 44% of pts. Conclusions: The majority of pts on treatment after 4 yrs continue on the QD dosing schedule. Long-term follow-up of dasatinib 100 mg QD further demonstrates durable efficacy and a generally better tolerated safety profile for pts with CML-CP following prior imatinib therapy.