TY - JOUR
T1 - Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for philadelphia chromosome-positive leukemia
AU - Hughes, Timothy P.
AU - Laneuville, Pierre
AU - Rousselot, Philippe
AU - Snyder, David S.
AU - Rea, Delphine
AU - Shah, Neil P.
AU - Paar, David
AU - Abruzzese, Elisabetta
AU - Hochhaus, Andreas
AU - Lipton, Jeffrey H.
AU - Cortes, Jorge E.
N1 - Funding Information:
This analysis was supported by funding from Bristol-Myers Squibb. The Bristol-Myers Squibb policy on data sharing may be found at: https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html. Professional medical writing and editorial assistance was provided by Samantha L. Dwyer, PhD, and Jessica Franciosi, PhD, of StemScientific, an Ashfield Company, part of UDG Healthcare plc, funded by Bristol-Myers Squibb.
Publisher Copyright:
© 2019 Ferrata Storti Foundation.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85059252438&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059252438&partnerID=8YFLogxK
U2 - 10.3324/haematol.2018.188987
DO - 10.3324/haematol.2018.188987
M3 - Article
C2 - 30093398
AN - SCOPUS:85059252438
SN - 0390-6078
VL - 104
SP - 93
EP - 101
JO - Haematologica
JF - Haematologica
IS - 1
ER -