Background: At 18 months (mos) of follow-up in the randomized phase 3 DASISION trial of dasatinib vs imatinib (IM) in newly diagnosed CML-CP, dasatinib continued to show superior efficacy and acceptable safety/tolerability (Shah et al. Blood 2010; 116: abs 206). Although fluid retention was more frequent with IM, pleural effusion was only seen with dasatinib. Here, pts with drug-related pleural effusion are analyzed retrospectively and management methods are discussed. Methods: In DASISION, pts received dasatinib 100 mg once daily (QD) or IM 400 mg QD. Pts with baseline pleural effusion were excluded. Chest x-rays were performed at baseline and after 6 mos, or more frequently if indicated clinically. Pleural effusions were graded according to CTCAE v3.0 criteria. Results: After 18 mos median treatment duration, 31/258 dasatinib-treated pts had a pleural effusion (12%; 3% grade 1, 9% grade 2, <1% grade 3). Pts with pleural effusion were older (median age 59 vs 44 yrs). In pts with (n=31) vs without (n=227) pleural effusion, Hasford risk score was intermediate in 68% vs 45% and high in 10% vs 20%, and median dasatinib dose was 93 vs 100 mg/d. Most effusions (87%) occurred beyond 8 weeks of treatment (median time to event: 33 weeks). Pleural effusions were managed by dose modification (interruption in 24 pts; reduction in 13 pts) and/or medical intervention (diuretics in 13 pts; corticosteroids in 11 pts; therapeutic thoracentesis in 3 pts). 4 pts (1.5%) discontinued therapy due to pleural effusion. To date, most effusions (84%) have not recurred. Based on consensus from an expert panel, a management algorithm will be presented. Of pts with pleural effusion, 94% and 65% achieved a complete cytogenetic response and major molecular response, respectively (vs 84% and 56% in pts with no pleural effusion). In pts with or without pleural effusion, peripheral lymphocytosis was noted in 42% vs 19%. Conclusions: At 18 mos in pts receiving first-line dasatinib in DASISION, pleural effusion was predominantly mild to moderate in severity, more commonly associated with lymphocytosis, managed by dose modification and/or medical intervention, and did not appear to impact efficacy.