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

Timothy P. Hughes, Pierre Laneuville, Philippe Rousselot, David S. Snyder, Delphine Rea, Neil P. Shah, David Paar, Elisabetta Abruzzese, Andreas Hochhaus, Jeffrey H. Lipton, Jorge E. Cortes

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages93-101
Number of pages9
JournalHaematologica
Volume104
Issue number1
Early online date9 Aug 2018
DOIs
Publication statusPublished - 2019

Keywords

  • Journal Article

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for philadelphia chromosome-positive leukemia. In: Haematologica. 2019 ; Vol. 104, No. 1. pp. 93-101.
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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.",
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Hughes, TP, Laneuville, P, Rousselot, P, Snyder, DS, Rea, D, Shah, NP, Paar, D, Abruzzese, E, Hochhaus, A, Lipton, JH & Cortes, JE 2019, 'Incidence, outcomes, and risk factors of pleural effusion in patients receiving dasatinib therapy for philadelphia chromosome-positive leukemia', Haematologica, vol. 104, no. 1, pp. 93-101. https://doi.org/10.3324/haematol.2018.188987

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

In: Haematologica, Vol. 104, No. 1, 2019, p. 93-101.

Research output: Contribution to journalArticle

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AU - Rea, Delphine

AU - Shah, Neil P.

AU - Paar, David

AU - Abruzzese, Elisabetta

AU - Hochhaus, Andreas

AU - Lipton, Jeffrey H.

AU - Cortes, Jorge E.

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