1. Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for Philadelphia chromosome-positive leukemia
- Author
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Hughes, Timothy P, Laneuville, Pierre, Rousselot, Philippe, Snyder, David S, Rea, Delphine, Shah, Neil P, Paar, David, Abruzzese, Elisabetta, Hochhaus, Andreas, Lipton, Jeffrey H, and Cortes, Jorge E
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Orphan Drug ,Pediatric Research Initiative ,Pediatric ,Clinical Trials and Supportive Activities ,Hematology ,Childhood Leukemia ,Pediatric Cancer ,Rare Diseases ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Dasatinib ,Disease-Free Survival ,Female ,Humans ,Incidence ,Leukemia ,Myelogenous ,Chronic ,BCR-ABL Positive ,Male ,Middle Aged ,Pleural Effusion ,Malignant ,Risk Factors ,Survival Rate ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - Abstract
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. clinicaltrials.gov identifier 00481247; 00123474.
- Published
- 2019