Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia

• Published in: Haematologica (Roma) Vol. 104; no. 1; pp. 93 - 101
• Main Authors: Hughes, Timothy P., Laneuville, Pierre, Rousselot, Philippe, Snyder, David S., Rea, Delphine, Shah, Neil P., Paar, David, Abruzzese, Elisabetta, Hochhaus, Andreas, Lipton, Jeffrey H., Cortes, Jorge E.
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.01.2019
• Subjects: Adult; Dasatinib - administration & dosage; Disease-Free Survival; Female; Humans; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Middle Aged; Pleural Effusion, Malignant - drug therapy; Pleural Effusion, Malignant - mortality; Pleural Effusion, Malignant - pathology; Risk Factors; Survival Rate
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2018.188987

Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, both as first-line therapy and after imatinib intolerance or resistance. While generally well tolerated, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors, and outcomes associated with pleural effusion were assessed in two phase 3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11 trials that evaluated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib (including DASISION and 034/Dose-optimization). In this largest assessment of patients across the dasatinib clinical trial program (N=2712), pleural effusion developed in 6-9% of patients at risk annually in DASISION, and in 5-15% of patients at risk annually in 034/Dose-optimization. With a minimum follow up of 5 and 7 years, drug-related pleural effusion occurred in 28% of patients in DASISION and in 33% of patients in 034/Dose-optimization, respectively. A significant risk factor identified for developing pleural effusion by a multivariate analysis was age. We found that overall responses to dasatinib, progression-free survival, and overall survival were similar in patients who developed pleural effusion and in patients who did not. .