Dasatinib lack of cross intolerance to imatinib in patients (pts) with chronic myelogenous leukemia chronic phase (CML-CP) intolerant to imatinib: a retrospective analysis of safety.

7015 Background: Dasatinib is a second generation BCR-ABL inhibitor structurally unrelated to imatinib. Dasatinib is effective in CML-CP patients intolerant of imatinib and is generally well-tolerated. Fluid retention, gastrointestinal intolerance, and myelosuppression are the most common adverse events (AE) and are dose and schedule dependent. These analyses were undertaken to explore whether the type of intolerance to imatinib predicts the safety of dasatinib.,Data from two multicenter studies in CML-CP (one Phase II and one Phase III) were pooled. Intolerance to imatinib was defined as ≥ Grade 3 non-hematologic toxicity and/or Grade 4 hematologic toxicity lasting > 7 days. Dasatinib doses were 70 mg BID, 50 mg BID, 100 mg QD and 140 mg QD. Median duration of dasatinib therapy was 11.96 mos (0.03-30.06 mos). Discontinuations due to NCI-CTCAE Grade 3-4 toxicities were used to assess cross intolerance between imatinib and dasatinib. Correlation between pleural effusions on dasatinib and fluid retention on imatinib was assessed.,A total of 271 imatinib-intolerant CML-CP patients (pts) were included. Duration of imatinib therapy was < 1year in 58% of pts. Imatinib intolerance (im- I) was hematologic in 46 pts and non-hematologic in 225 pts (exact cause known in 210 pts.). A total of 9 (4%) pts experienced the same Grade 3-4 non-hematologic toxicity on dasatinib as on imatinib and only 2 (1%) discontinued dasatinib; the other 7 pts continued dasatinib after dose reduction. Of the 10 pts with fluid retention on imatinib, none developed pleural effusion on dasatinib. Among the 46 pts who discontinued imatinib for hematologic toxicity, 6 (13%) discontinued dasatinib because of cytopenia.,There was no evidence of cross-intolerance between imatinib and dasatinib in this large population of imatinib-intolerant CML-CP pts. [Table: see text] [Table: see text].