Pleural Effusion in Patients (pts) with Chronic Myelogenous Leukemia (CML) Treated with Dasatinib after Imatinib Failure.

Dasatinib (SPRYCEL^®, BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL with significant activity in CML after imatinib failure. Dasatinib is well tolerated. The most frequent non-hematologic toxicities are gastrointestinal, rash, and fluid retention syndromes. We evaluated the incidence and outcome of pleural effusion among 131 pts with CML treated in phase I (n=50) and II (n=81) studies of dasatinib after imatinib failure or intolerance at our institution. The median age was 59 years (range, 19 to 81). Sixty-one (47%) pts were in chronic (CP), 30 (23%) in accelerated (AP), and 40 (30%) in blast phase (BP). The daily dose of dasatinib was <70 mg in 15 (11%; 8 bid, 7 qd) pts, 100 mg in 20 (15%; 10 bid, 10 qd), 140 mg in 87 (67%; 66 bid, 21 qd), and >140 mg in 9 (7%; 6 bid, 3 qd). Dasatinib was administered for a median of 42 wks (range, 4 to 120 wks). Pleural effusion occurred in 41 (31%) pts; it was grade 3–4 in 17 (13%). The median time to its development was 5 wks (range, 1 to 107). Effusion occurred in 34% of pts in CP, 34% in AP, and 32% in BP. Effusions were categorized according to the volume of lung involvement: grade 1 (<10% of one lung) occurred in 7 (17%; 5% of total) pts, grade 2 (11–25%) in 17 (42%; 13% of total), grade 3 (26–50%) in 13 (32%; 10% of total), grade 4 (51–75%) in 3 (7%; 2% of total), and grade 5 (> 76%) in 1 (2.5%; 0.7% of total) pt. Grade ≥ 3 effusion occurred in 6 pts with CP and in 11 with advanced phase CML (5 AP, 6 BP). Effusion was more frequent among pts receiving daily doses ≥ 140 mg compared to those treated at < 140 mg (34 of 41 [83%] vs 7 of 41 [17%]; p<0.0001). Effusions were bilateral in 78% and exudative in 78% of pts. Dasatinib was interrupted in 33 (80%) and dose-reduced in 29 (71%) pts. Effusion recurred in 10 (24%) of 41 pts, leading to more than one treatment interruption. Effusion was managed with diuretics in 71%, steroids in 27% (steroids plus diuretics in 12%), thoracentesis in 22% of pts and chest tube in 5%. Dasatinib was permanently discontinued due to recurrent effusion in only 3 pts. In conclusion, pleural effusion is a not uncommon, but manageable complication of dasatinib therapy, particularly among pts in advanced phases of CML receiving dasatinib doses ≥140 mg. In most cases, early identification, temporary dasatinib interruption, the use of diuretics and/or pulse steroids, and subsequent dasatinib dose reduction led to rapid resolution.